Microbiome and gut health
Apr
04
Know your poop, it can tell you a lot

It’s time for a poop talk.
I always ask my clients about their bowel movement. I realize it’s not the most comfortable question but poop can be an important marker of health or disease. It can tell you a lot. Is it soft, hard, smelly, yellowish, back, fatty, with mucus, with blood or with undigested foods? Next time you poop, pay attention to what comes out!
We can observe our body, our body fluids (blood) and our body secretions (urine, feces, saliva) for signs of dysfunction. Some parameters can only be measured by a laboratory but you can also be your own detective and learn how to distinguish a healthy bowel movement from an unhealthy one.

What you need to look at in terms of poop?
Color, consistency and smell are the key parameters.
Normal, healthy poop is brown (from light brow to dark brown), well-formed (sausage like) and has no repelling smell.

What’s your poop color like?
Healthy human feces is brown. The color can change after eating some foods (red beets, spinach), after taking certain medications (iron for example) or it can also be an indication of a health issue.
- Black or a very dark color can be related to the use of certain medications, supplements (iron, activated charcoal), foods (black barriers, red wine). It can also indicate a blood loss from stomach or (small) intestine, or can be a sign of inflammation, ulcer, polyps, or cancer. Constipation may promote darker stools. A black stool with a very strong abdominal pain can indicate an internal bleeding.
- Red, eating red beets can color your stool red.
- Green, if you eat a lot of green vegetables your poop can turn green.
- Grey – light color, can indicate that there is no bilirubin (color compound) present in a bile or/and too high fat intake. It can be caused by impaired bile production/storage, intestinal infection, reactivity to foods, pancreas problems, low gastric acid, resulting in impaired digestion. Noteworthy, if you suddenly change your diet by for example following a low carb diet and will be eating more fat, your stool may have lighter color especially in the beginning. It’s related to the fact that if you eat more fat - your body needs more bile and sometimes it needs some time to adjust and to produce more bile.
- Bloody, most of the time caused by rectal/anal bleeding such as hemorrhoids.
- Yellow, often occurs together with a soft stool/diarrhea and intense smell. It can be related to a quick intestinal passage, lack of bile. Bile contains bilirubin which turns your feces brown. Possible causes of yellow stool include gluten intolerance, infection (Salmonella/Clostridium), use of medicines, alcohol consumption, liver and/or bile dysfunction, bile stones. Quick intestinal passage can promote nutrient malabsorption. Babies may have yellow poops.

What’s your poop smell like?
Normal fecal matter can smell as a result of intestinal bacterial fermentation and the presence of dead intestinal microbes. However when the smell of your poop is very intense – it stinks – or it has other than a regular smell it should raise a red flag. It can be a sign of intestinal infection (parasites bacteria), impaired digestion (specially of proteins), intestinal inflammation, food allergy or food intolerance. Sour smell can indicate a low fecal pH, yeast overgrowth and/or overconsumption of starch. If you let stinky gases, of rotten eggs, then think of putrefaction and sulphur release. If your stool stinks and has a “pap-like” consistency – it may indicate a medical condition.

What’s your poop consistency like?
Normal feces has a sausage like shape and the consistency which is not too hard and not too soft – just right. If this description does not fit your poop, please read on. Note, that some people may experience changing stool consistency from too soft to too hard.
*Chronically “Pap-like”, your poop is soft and not well formed. It can stick to the toilet and you need to use a lot of toilet paper to wipe yourself well. The pieces of the feces can float. The most common causes of a “pap-like” stool include parasitic infection (such as Dientoamoeba fragilis), intestinal dysbiosis for example after antibiotic use (candida overgrowth), food intolerance (histamine, lactose, gluten), low gastric acid, pancreatic issues, or medicine use.
*Chronically too hard, a slow bowel movement with a sausage-like but lumpy stool, or separate hard lumps like nuts. For constipation the frequency can be once in 3 days or less. Often there is a feeling of pressure to go to the toilet yet you can’t poop. Hard feces and constipation is more prevalent in women and in overweight individuals. Constipation can be related to a slow intestinal passage which can be a result of holding the stool for too long, for example children and teachers at schools, car drivers may have this tendency. Overweight, intestinal parasites, food allergy, pregnancy, underactive thyroid, gluten intolerance, medicine (codeine, anti-depressives, anti-histamine) use, supplements (iron), genetic predisposition, intestinal physiology, sometimes dehydration and too little dietary fiber (fruits and vegetables) can contribute to constipation and hard stools.
*Chronically too watery, diarrhea. Diarrhea is watery, unformed feces that you can’t keep in. You can have acute or chronic diarrhea. With acute diarrhea complaints should resolve by itself within few days. Chronic diarrhea takes more than 3 weeks. Chronic diarrhea can be accompanied with fecal mucus and blood. Chronic diarrhea can also alternate with the episodes of normally formed stools or constipation and hard stools. Chronic diarrhea increases the risk of dehydration and loss of electrolytes, therefore remember to drink adequate amount of water if you suffer from chronic diarrhea. Chronic diarrhea can be caused by a chronic bacterial infection or a post-infectious syndrome, parasites, food intolerance (gluten, histamine, lactose, fructose), food allergies, intestinal inflammation, auto-immune disease, pancreatic and bile problems, nickel or latex allergy, intestinal dysbiosis (after antibiotic), additives to foods, or cancer.

Fatty poop?
Normal feces contains fat, about 0-4 gram fat per 100 gram poop. If there is more fat or you can’t digest fat properly, your stool will be fatty, shiny and will stick to the toilet surface. Fatty stool can also stink more or has a lighter color. If your stool is fatty consider following issues: low gastric acid, impaired pancreatic function, bile or liver issues, celiac disease, alcoholism, bacterial or parasitic infection, intestinal inflammation (Crohn disease, Colitis ulcerosa), or over consumption of nuts. Fat malabsorption can cause malabsorption of fat soluble vitamins such as vitamin D, E, A or K.

Mucus?
Fecal mucus comes from intestinal mucosal membranes. Normal and well-formed feces contains no visible mucus. If you do see mucus around your stool or within it, it may indicate inflammation or irritation of the intestinal lining. Bloody mucus will indicate inflammation. With constipation and inflammatory bowel diseases there may be more mucus formation/secretion.

If your feces is off and you can’t identify the reason, do a fecal analysis to begin with.

Diseases, Microbiome and gut health, Nutrition
Feb
28
Abdominal bloating nightmare

Many people suffers from abdominal bloating and if you are one of them you know that’s no fun. Majority of people that come to see me struggles with it, therefore I decided to give it a brief attention. If bloating interferes with your daily life, your work, your social of recreational activities, it’s something you need to look into.

Symptoms

Your abdomen feels bloated when your GI tract increases its volume due to presence of air or gas. It is a nasty feeling of fullness, swelling, tightness, or hardness. You may also experience pain, flatulence, abdominal distension, nausea, burping, belching, or gurgles. Some people feel like they “look pregnant” when bloating strikes.

What are the most common causes of abdominal bloating?

There can be various causes of being bloated, some of which are quite easy to tackle and some may need a professional help.

Consider following if you feel regularly bloated:

Eating and drinking too fast. Eating too much. When you eat and drink fast you may swallow too much air and promote gas formation, also rushing while eating impairs digestion. Chewing gum, smoking may also worsen the problem. Our digestive system has certain capacity to digest efficiently, if we eat too much food (too fast) it will obviously not be able to digest optimally. Eat slowly, not too much and chew your food thoroughly for better digestion.

Diet rich in starch and/or nuts. Overconsumption of starch (grains), nuts, processed foods, sugar, difficult to digest meal combinations such as high starch and high protein content in one meal. Overconsumption of starch intensifies the complaints related to candida and intestinal parasites.

Low gastric acid & indigestion. Low gastric acid and/or deficiency of digestive enzymes can result in abdominal bloating. I write about low gastric acid here.

Microbial GI dysbiosis. When your gut microbes get out of balance resulting in dysbiosis (beneficial and bad microbes are out of balance), the bloating may occur. Think of candida (Candida albicans) or other yeast overgrowth, parasitic infection (Dientamoeba fragilis or Blastocystis hominis), gastric Helicobacter pylori infection, or small intestinal bacterial overgrowth (SIBO).

Food Intolerance (lactose, histamine, fructose). People with inability or decreased ability to break down lactose (milk sugar), fructose or histamine may feel bloated.

Reactivity to gluten. You may feel bloated when your body does not tolerate gluten, sometimes it’s just too much gluten in your diet and sometimes it is a non-celiac gluten sensitivity or a celiac disease.

Crohn disease or ulcerative colitis. People with intestinal inflammation such as in Crohn disease or ulcerative colitis may experience abdominal bloating as well.

Impaired pancreatic function or bile production. Pancreatic -under or -overactivity, too little or too much bile can influence digestion of fats, starch and as a result aggravate the abdominal bloating.

Constipation. If you have a bowel movement only every few days, your abdomen will have a tendency to bloat because of an increased abdominal pressure.

Dehydration. The more dehydrated your body is, the higher chance you may feel bloated. Drinking too much alcohol, too little water and eating salty snacks can promote bloating.

Hormonal Changes such as during PMS and period. Due too hormonal changes and hormonal imbalances many women tend to feel bloated before and/or during their period.

Abdominal Water retention. Abdominal water retention called ascites takes place when fluid fills the space between the lining of the abdomen and the organs. It usually occurs as a result of liver problems.

What can you do?

Find the root cause.

First, you can experiment yourself by eating slowly, chewing properly, avoiding drinking with meals, eliminating processed and junk foods, eliminating sugar and starch rich foods, excluding diary, gluten, or histamine rich foods. If after your detective work you still experience abdominal bloating, get yourself tested. I would suggest starting with a fecal analysis that would include your microflora profile, parasites, digestion profile, inflammation markers, gluten reactivity markers, pancreatic elastase, bile salts, histamine) and a blood test.

For occasional bloating you can have a peppermint, ginger, fennel or chamomile tea, or other herbal remedies. Preferably avoid gassy fruits and vegetables, sodas, artificial sweeteners, sugar, starch, gluten and diary.

Diseases, Microbiome and gut health, Nutrition
Jan
11
Stomach acid

I want to share with you some stomach acid know-how essentials. It may surprise you that many health issues, not only digestive ones, are related to low stomach acid. Many people who come to see me have low stomach acid. I used to have it as well, without realizing it. Changing my eating habits and using some of the tips below helped me to restore my gastric acid production and as a result to feel better.

Why do you need stomach acid for?

Gastric acid (hydrochloric acid HCl) found in your stomach facilitates digestive enzyme secretion and protein digestion. Your stomach (muscular sac) acts as a sort of blender breaking your food physically (churning action of the stomach muscle) and enzymatically (the right gastric pH and activity of digestive enzymes). Low pH (1,5-2,5) of gastric acid is essential for digestive enzymes to become active and to digest. Apart from facilitating digestion, we need gastric acid as a first line of defense against food poisoning (Campylobacter, Salmonella), parasitic (Giardia, worms), bacterial (Helicobacter pylori, Small Intestinal Bacterial Overgrowth), and fungal (Candida) infections. Without adequate acid, we do not digest our food, we are at risk of mineral and vitamin deficiencies, and we are more vulnerable to various infections. Low stomach acid compromises our immunity. Therefore, you need stomach acid and it’s good for you.

Low stomach acid (hypochlorhydria) has been associated with many common health problems.

What symptoms to look for in association with low gastric acid?

  • Bloating, burning, burping, and flatulence right after meals
  • Abdominal fullness after meals
  • Poor appetite
  • Stomach upsets easily
  • Diarrhea or constipation 
  • Undigested food in stool
  • Nausea after taking supplements
  • Reactivity to foods (food allergies, food sensitivities)
  • Iron deficiency
  • Chronic intestinal infections
  • Chronic candida infections
  • Acne
What symptoms to look for in association with low gastric acid?

What can you do about low gastric acid?

Improve your digestion and restore your gastric acid production.

Imagine that if you are not able to properly digest your food and absorb the nutrients, cells within your body will not get the fuel, the nutrients they need for proper functioning. Because of impaired digestion and absorption you may experience some health issues. Digestion process starts even before you eat. When you see food, smell it, or think about it your senses are triggered, your brain is triggered, your digestive system is triggered. You may start producing saliva, gastric acid, hormones, and other molecules to prepare you for a meal. This is how digestion process begins.

Compare it with a scenario when you sit on a coach in front of TV, and while watching an interesting move you pop something in your mouth without realizing what and without realizing you eat. How well will your digestive system be prepared then to perform the task of digestion? Expectedly, not that well as if you eat mindfully.

It reminds me of something. One of my former colleagues years back, an Indonesian women, was always eating very mindfully. She was eating slowly and chewing her food very well. When she indulged few bites of her meal, my meal had already vanished. I was eating like it was a race and it always stroke me why she was eating so slowly, too slowly I thought then. But she simply knew that to digest well you need to eat well. In cultures where food sources are limited, people tend to eat more mindfully and slowly. They chew every single bite very well simply to extract as much nutrients as possible and to properly switch the digestive machinery on. Sound simple to do, right? Yet, in the current era of constant rush and stress it can be quite a task to do. Let me provide some guidelines that can change how you feel.

How can you digest better?

  • Chew your food thoroughly. Proper chewing is essential in order to promote gastric acid production and digestion. Try to chew your foods 20-30 times before swallowing. Eat smaller meals so the body can process your food properly and has possibility to heal. You may consider fasting or intermittent fasting as an additional boost for your general health and stomach. Part of your body healing is letting it recover. If you’re continually eating food from morning to sundown every day, your body doesn’t have the time to recover and heal.
  • Eat mindfully and relax. Relaxation promotes digestion whereas stress inhibits digestion.
  • Add bitterness to your menu. Include bitter herbs, bitter foods and bitter drinks. Bitterness increases secretion of saliva, gastric acid, pepsin, bile, and digestive enzymes so all we need to digest properly. Check your health-food stores for bitter/digestive herbal teas or bitter tinctures (Swedish bitters).
  • Drink adequate amount of (salty) water. Drink water with sea salt/Himalayan/Celtic salt every day to promote healthy gastric lining. You can mix 1-1,5 liter of (purified) water with about 1-1,5 gr of salt and drink it through the day (best after waking up, 30 min before lunch and before dinner, and before going to bed).
  • Avoid drinking (large quantities) during meals or shortly after your meals.
  • Have Apple cider vinegar (ACV). Some people find that ACV makes wonders for their digestion. Drink about 50-100 ml of water with 1-2 tablespoons of ACV 15-20 min before your (protein) meals. You can also add some ACV to your salads. You may need to gradually increase the amount of vinegar until you get the desired effect. Note: do not use ACV if you have histamine intolerance.
  • Take Digestive enzymes. Another help is to take digestive enzymes prior meals, also possible to take them with the apple cider vinegar. Digestive enzymes will help breaking down the nutrients (protein, fat, carbohydrates) you take in. Too high stomach pH does not allow for efficient food (protein) digestion. Take the enzymes until your stomach acid balances out.
  • Add betaine HCL (with Pepsin) with protein rich meals. If above tricks do not work, consider taking betaine HCL (with pepsin). Now, the trick with betaine HCL is you want to take the right amount, always start off with one capsule and see how you feel. Gradually increase the dosage from 300-750 mg to 1000-2000 mg per meal. When you get warmness/discomfort in your stomach, cut back by one capsule per every next meal. If you feel discomfort because of too high betaine HCl intake, you can neutralize the acid by drinking water or milk with 1 teaspoon of baking soda. Some people need one capsule; other people may need to take up to few capsules of betaine HCl. Once you have established a dose, continue this dose. It may however change over time as your digestion is improving, so stay vigilant and decrease the dosage when needed. With smaller meals, you may require less betaine HCl. Take betaine HCl only if you’re eating protein dense meals (with meat). Important: if you feel discomfort (heartburn) at the lowest dose of betaine HCl, it suggests you have a healthy response, no issue with low stomach acid and no need to take betaine HCl.
  • Try umeboshi plums. Umeboshi plums are salted and pickled plums helpful to relief indigestion. You can get them in Asian food stores, use them as umeboshi vinegar, as the base for tea or add as a salad dressing instead of salt and vinegar. ‘
  • Try acupuncture and/or chiropractic care.
  • Avoid processed foods and overeating.

Antacid?

Many people think they have too much stomach acid and therefore they take antacids. Antacids may relief some symptoms but most of the time the problem is not in too much acid in your stomach but in the fact that your stomach acid may just be in the wrong place, where it does not belong such as in esophagus. It may lead to acid reflux. I realize that the symptoms of too much and too little acid are similar, such as belching, burping, feeling of fulness after meals but be aware that too low acid is most of the time to blame for the symptoms described above.

Low stomach acid may be caused by pernicious anemia, chronic Helicobacter pylori, long-term term treatment with proton-pump inhibitors, autoimmune gastritis, or stress.

If your symptoms do not resolve after applying provided here tips, do consult it with you physician.

Diseases, Microbiome and gut health
Apr
05
Why bile matters? The magic of BILE: fat digestion and detox

Do you have any of the following symptoms?

Fatigue, constipation/diarrhea, incomplete digestion/absorption of fats, headaches, light colored or/and fatty stools, gas and bloating, hormonal imbalances/thyroid disease, detox problems, sleep problems, ear ringing (tinnitus), nausea, bitter taste in the mouth, sciatica like pains, low serum albumin levels, decreased absorption of nutrients, growth failure in children, weight loss, gallbladder issues or your gallbladder was removed.

If yes, then read on.

Why do we need bile?

Bile is a soap-like substance vital for optimal (fat) digestion. It is a complex and unique aqueous product of the liver hepatocytes which is further modified by the activities of the bile duct epithelium. Then bile is collected, concentrated and stored in a gallbladder to be delivered to a small intestine when needed. Bile helps digesting fats and supports removal, flow and metabolism of various substances. Bile is composed in about 95% of water, the remaining constituents are bile salts, cholesterol, amino acids, bilirubin phospholipid, steroids, enzymes, vitamin, porphyrins, as well as heavy metals, environmental toxins, and drugs.

Without quality bile we are at risk of developing health issues as bile is critical for metabolic conversions and flow of vital nutrients as well as elimination of toxic substances:

  • Bile is a major route to excrete harmful substances, toxins
  • Bile salts function to emulsify dietary fats and facilitate their digestion and absorption
  • Bile helps eliminating cholesterol
  • Bile stimulates intestinal innate immune system and supports immunity by excreting immunoglobulin A (IgA), inflammatory cytokines
  • Bile is vital for chole- and entero-hepatic circulation
  • Bile is essential carrier for some hormones and some hormonal conversions, estrogens, vitamin D3 metabolite, prolactin or insulin are excreted with bile
  • Bile excretes vitamins (folate, B6, cyanocobalamin) and contains glutathione, glutamic acid, pheromones and other vital components
  • Bile helps make calcium and iron more absorbable

Common gallbladder and bile related complaints

Fat digestion may be impaired as a result of impaired digestive enzymes production and/or impaired bile production. Common symptoms include burping, bloating, nausea after high-fat meals. Impaired fat digestion contributes to malabsorption of fat soluble vitamins (A, E, D, K). In addition, gallstones can form and typically they are a result of saturation and precipitation of bile component(s) such as cholesterol, pure pigment of calcium bilirubinate, or minerals. Gallstones may be asymptomatic or cause biliary colic with regular pain free intervals of days or months. Real-time ultrasonography is used to diagnose gallstones.

How to support bile production?

Number one is to eat anti-inflammatory real foods, mostly plants and avoid pro-inflammatory processed foods, access sugar and fried foods.

You need nutrients from real foods in order to produce bile, a package of chips will not provide them.

DIET: Include diversity of dietary fiber rich foods such as (raw) vegetables and fruits in your diet as a source of valuable nutrients for you and prebiotic fiber for your gut microbiota. Your liver and bile will benefit from eating cholagogic foods like artichoke, dandelion greens (leafy greens), radish, chicory, from bitter tasting foods, as well as potassium rich foods such as avocado, tomatoes, sweet potatoes, banana and from eating sprouted seeds and nuts. Some of the important components supporting bile production include choline (eggs, meat, shrimps, fish, chicken, shitake), taurine (fish, meat), betaine (beet root, spinach, quinoa, amaranth), vitamin C (fruits and vegetables), vitamin E (dark leafy greens, almonds, sunflower seeds, avocado, olive oil). Worth to mention is that our gut microbiota is involved in bile acids metabolism and formation, therefore taking care of these little gut creatures by feeding them prebiotic rich foods is of importance.

Some people experience a significant improvement after elimination of eggs, pork, onions, or milk from their diet because of the possible allergic component.

SUPPLEMENTS: You may consider supplemental and herbal support to improve liver health, decrease inflammation and promote bile production by including following: turmeric, milk thistle, dandelion root, artichoke, activated charcoal, lipase enzyme, bile salts or ox bile. Consult with your physician or nutritionist before start taking the supplements.

Last but not least, engage in regular physical activity and don’t forget that consumption of enough (six to eight glasses) water daily is necessary to maintain the water content of bile.

Sources:

  1. “Bile Formation and Secretion” James L. Boyer. Compr Physiol, July 2013, 3 (3); 1035-1078.
  2. “Gallstones” M. T. Murray. G Natural Medicine text book, fourth edition. J. Pizzorno & M Murray. Elsevier 2013.
  3. “Metabolism of Cholesterol and Bile Acids by the Gut Microbiota” Philippe Gérard. Pathogens 2014, 3, 14-24.
Microbiome and gut health
Nov
28
How gut bacteria can contribute to the extra weight

Linking the gut microbiota to obesity and diabetes

Have you ever envied skinny people who eat a lot of unhealthy foods yet remain slim-figured? People often say it’s because of genes or better metabolism, but that’s not the whole story! Whose metabolism are they talking about? The person’s metabolism or the metabolism of their gut microbes?

INTERESTED? First, let me explain that our intestinal microorganisms coevolved with us to support our physiology and our metabolism. Our body constantly communicates and cooperates with them. When our microbes, the so-called “internal garden,” are in a state of balance and when operate at peak efficiency, so do we and our metabolism. When things get out of balance and we suffer from microbial gut dysbiosis, it directly affects our health and our weight. To achieve and maintain a healthy weight it is essential to take care of our microbial selves. You may have, for example, difficulties in losing weight. Until you address your microbiome, you may be trapped in a vicious circle of dieting because you are missing an important player in a game — the gut microbiome. Let’s see how these microbes may contribute to weight control.

Gut microbes affect our energy harvest and storage

Recent studies indicate that gut microbes contribute to our energy harvest, storage, and spending. This process is optimal when the amount of energy extracted from the diet equals the amount used, maintaining equilibrium. Over the course of evolution, animals have developed a smart strategy to protect energy reservoirs by forming fatty adipose tissue. However, once energy-dense foods erupted in western countries, we began to over-accumulate and over-stimulate this energy, which can result in obesity. It has been found that multiple factors, such as genetics, diet, sedentary lifestyle, or hormonal imbalance, may contribute to the development of and progression of obesity. In addition, recent scientific findings bring to light the role of the gut microbiota and its influence on fat storage, glucose blood levels, or hormonal expression. Obesity and type 2 diabetes are characterized, among other features, by low-grade inflammation and alterations in intestinal permeability, called leaky gut. Inflammation is considered a significant obesity component.

Some obesity facts to digest

World Health Organization (WHO) recognizes the problem of a global obesity epidemic. Though once associated with high-income countries, it is now found across low- and middle-income populations. It strikes young and old, wealthy and poor. Overweight children are at higher risk to become obese adults and develop diabetes.

According to WHO (from January 2015):

  • worldwide obesity has more than doubled since 1980
  • in 2014, more than 1.9 billion adults, 18 years and older, were overweight, of which over 600 million were obese
  • 39% of adults aged 18 years and over were overweight in 2014, and 13% were obese
  • Most of the world's population lives in countries where being overweight kills more people than being underweight
  • 42 million children under the age of 5 were overweight or obese in 2013
  • 1 in 3 children at the age of 11 is overweight or obese

As a consequence, there is a worldwide increase in the prevalence of obesity-associated diseases, such as insulin resistance, hypertension, type 2 diabetes, cardiovascular disease, end-stage renal disease, and non-alcoholic fatty liver disease. Diabetes mellitus (DM) affects about 347 million people worldwide.

An interplay between obesity and inflammation

Inflammation is a key component of obesity-associated diseases. Higher levels of certain inflammatory markers have been found in obese individuals. Some of the inflammatory markers include C-reactive protein, erythrocyte sedimentation rate, inflammatory cytokines, and plasminogen-activator inhibitor 1. However, connecting the dots between obesity, inflammation and the risk of disease remains to be unknown. Scientists are trying to put the obesity puzzle pieces together by studying the complex network of gut microbiota (microorganisms), the intestinal lining (mucosa), and the gut-associated lymphoid tissue. Below you will find the latest findings in this field of research.

Obesity and the intestinal microbiota

Our intestinal tract harbors between 500 — 1000 microbial species and this microbial population is commonly called the gut microbiota. There are three dominant bacterial phyla; Bacteroidetes ( eg. Bacteriodes spp), Firmicutes (eg, Bacillus and Clostridium spp), and Actinobacteria (eg. Bifidobacterium spp). These gut microbes are involved in energy metabolism and therefore are important to consider when talking about obesity. Very interesting results were found from animal studies, with germ-free mice having lower body mass and body fat in comparison to germ-inhabited, or “normal” mice. Moreover, transplantation of “normal” microbiota to germ-free mice led to normal bodyweight found in germ-inhabited mice. Even more interesting were the findings of the microbial transplant performed from obese mice to germ-free mice; for whom an increased fat mass was recorded. Further animal studies indicated that the bodyweight can be partly determined by the gut microbiota as well as by the diet.

Human studies looking at the gut microorganisms of obese and lean individuals reveal that lean humans and animals have different microbial gut composition than the obese ones, with a lower microbial diversity in obese subjects. More specifically, some obese individuals, in comparison to lean individuals, were shown to have higher relative abundance of bacterial Firmicutes species with lower relative abundance of Bactoroidetes bacteria. Contrary to obese people, lean people tend to have higher diversity of microbial species in their gut and are often found to have more microbial life of Bacteroidetes bacteria, which utilize plant polysaccharides as a source of energy. Other studies, however, showed conflicting results or no significant difference in the microbial gut composition, but did show greater diversity in lean individuals. There is some controversy around the Firmicutes/Bacteroidetes ratio as an obesity or obesity-risk indicator. For example, my gut microbial fingerprint (sample analysis done by uBiome) showed relative high abundance of Firmicutes, characteristic for obese individuals, but I am a lean person. We know however, that the composition, such as low diversity, of the gut microbiota early in life may predict the subsequent development of obesity or being overweight. Interestingly, there is a bacterium called Akkermansia muciniphila that resides in mucus layer of human intestinal lining which tends to be less abundant in obese individuals. Several studies have indicated its potential in reducing inflammation and therefore possibly protecting against the development of obesity and type 2 diabetes.

Our food shapes the composition of our microbial gut companions

There are studies looking at the effect of diet on the microbial gut fingerprint. For example, increased daily caloric intake (2400 kcal vs 3400 kcal with similar macronutrient intake ratios) resulted, after only 3 days, in greater abundance of Firmicutes and lower abundance of Bacteriodetes. Another study investigating the impact of high-fat diet recorded the gut microbiome changes as early as one day after a new diet initiation. Low- or high-carbohydrate, high-protein, plant- or animal-based, high- or low-fat — all different diets influence and modulate, in  a more or less favorable way, the gut microbiome.

The appetite regulation by a hunger stimulating hormone, ghrelin, has been shown to be influenced by presence or absence of Helicobacter pylori. Some studies indicated that H. pylori eradication was linked to increased ghrelin levels, which could perhaps explain increased appetite and weight gain following H. pylori eradication. Western populations have largely eradicated this bacterium from their lives — could this also contribute to obesity? And what about the effect of antibiotic use on weight gain in humans and livestock? It should not be underestimated when facing a global obesity epidemic.

Endotoxin – an important player in metabolic inflammation

Let's talk for a moment about the intestinal permeability (leaky gut) and short-chain fatty acids. Although their role in obesity specifically is not yet entirely clear, they certainly are of importance. For more information about the intestinal permeability, please check my article on a leaky gut. Noteworthy, when dealing with a leaky gut, gut-derived metabolic endotoxaemia may occur, which can increase the risks of obesity associated-diseases, such as cardiovascular disease or type 2 diabetes. Metabolic endotoxaemia, also called circulating endotoxin, takes place when increased concentrations of bacterial (Gram-negative) endotoxin, also called lipopolysaccharides (LPS), enter the blood as a result of impaired epithelial tight junctions with an increased intestinal permeability (leaky gut). LPS also circulates, at low concentrations, in the blood of healthy individuals. Chronic bacterial translocation, resulting in circulating LPS due to increased intestinal permeability, may trigger inflammation and an immune response, causing a persistent low-grade inflammation typically found in obese individuals. In animals and humans, consumption of high-fat foods was shown to result in increased levels of endotoxins (LPS) in the blood and an altered composition of the gut microbiota.

A few words about short-chain fatty acids (butyrate, acetate, and propionate): they are produced by bacterial fermentation of non-digestible dietary fiber, largely in our colon. They, mainly butyrate, support the intestinal lining integrity, serve as the energy source for colon epithelial cells, increase fluid and electrolyte uptake, promote blood flow and the secretion of gut hormones, stimulate mucin release, and exert profound immunometabolic effects. For example, butyrate-producing bacteria, Roseburia intestinalis and Faecalibacterium prausnitzii, are present at lower concentrations in individuals with type 2 diabetes than in healthy individuals.

What about the Fecal Microbial Transplantation (FMT)?

More and more fecal microbial transplants are performed, typically in individuals suffering from Clostridium difficile infection. A small-scale fecal microbial transplant study was conducted with lean male donor in insulin-resistant males with metabolic syndrome. As a result, there was a significant improvement in insulin sensitivity and increased intestinal microbial diversity, with more butyrate-producing bacterial strains, such as Roseburia. These results are promising, but we need more studies to have a better understanding of the ability to control the process and avoid possible unwanted effects of FMT.

Metabolic diseases are caused by multiple factors, such as high consumption of energy-rich foods, limited physical activity, age, or genetic factors. There is a growing array of interesting findings regarding the gut microbiota in obesity and obesity-related diseases. Yet, the controversy persists as to what degree gut microorganisms contribute to obesity. I think the complexity of the microbiota and its interaction with its host makes it very challenging to get clear answers. However, there is certainly an interplay between the gut microbiota, intestinal permeability, diet, and the immune system that shapes the development and progression of obesity and obesity-associated diseases, including type 2 diabetes. Manipulation of the intestinal microbes, by dietary changes, prebiotics, probiotics, or the more radical methods of fecal microbial transplant (FMT) or Roux-en-Y gastric bypass may serve as supportive avenues to obesity management.

Sources:

“Obesity, Inflammation, and the Gut Microbiota.” Cox at el., Lancet Diabetes Endocrinal 2015; 3: 207-215.

“Impact of the Gut Microbiota on the Development of Obesity: Current Concepts.” DiBiase et al, Am J Gastroenterol Suppl 2012; 1:22-27.

“Microbiota and Diabetes: an Evolving Relationship.” Tilg H and Moschen A, Gut 2014; 63: 1513-1521.

“Insights into the Role of the Microbiome in Obesity and Type 2 Diabetes.” Hartstra et al, Diabetes Care 2015; 38: 159-165.

“10 Facts on Obesity.” World Health Organization, 2015 January.

Suggested readings:

“The Microbiome Diet.” Kellman R, 2014.

“The Good Gut.” Sonnenburg J & Sonnenburg E. 2015.

Microbiome and gut health
Aug
14
Is your gut leaky?

Lets face it: exposure to certain factors makes our gut leak!

Scientists all over the world are working hard to unravel the puzzles on the growing incidence of many diseases, particularly in Western countries. It will take time before we get all the pieces together, but what we already know is that many diseases are linked to poor diet, gut dysbiosis, pollution, and stress, to name a few. Our Western diet has changed over the last two to three decades, from simple and unprocessed foods to highly processed foods with high sugar content. Coincidently, as we eat more processed foods, there is also a growing number of diseases, including autoimmune diseases. So the primary question arises: What’s the link between a poor diet and how our Westernized diet make us sick? Multiple factors are often involved, such as genetics, environment, lifestyle, and diet. They determine why some people get sick while others do not. Diet is undoubtedly a very important factor in our well-being. As Hippocrates stated “Let food be thy medicine and medicine be thy food.” Diet choice may have a profound effect on our health. Actually, a poor diet is one of the factors that has been linked to a leaky gut and consequently to diseases. Let’s find out what a so-called leaky gut is.

Intestinal barrier and intestinal permeability

What exactly stands behind a “leaky gut”? A leaky gut commonly refers to an increased permeability within the intestinal wall. This condition is sometimes called a “leaky gut syndrome.” Permeability allows certain molecules and ions to pass through the (intestinal) membranes. A leaky gut can be associated with food sensitivities, cramps, gas, bloating, and/or aches, pains, and diseases. To better grasp it, let’s define first “intestinal barrier” and “intestinal permeability.

Intestinal barrier refers to a complex intestinal structure of the digestive tract that includes vascular endothelium, the epithelial cell lining with tight junctions, and the mucus layer. It anatomically separates what’s within our digestive tube (microorganisms, food particles, or drugs) from what’s outside of it (immune cells, blood vessel, smooth muscles, enteric nervous system). The intestinal barrier serves to protect us from harmful staff such as microorganisms or toxins.

Intestinal permeability on the other hand, facilitating the passage between the inside (inner host) and the outside (lumen) of the intestinal lining, allows us to selectively absorb nutrients, liquids and to respond to the triggers present within the gut. Intestinal permeability is an intestinal barrier feature that selectively lets some molecules in and others out. Factors such as microbial gut imbalance, infections, some foods, exposure to chemicals, toxins, alcohol, or stress may alter-increase the intestinal permeability, as well as possibly damage the intestinal barrier by forming tissue lesions and punctures that could lead to a leakage –  a leaky gut. One of issue is it may lead to the translocation of undesired luminal gut content (microorganisms, toxins, gluten, undigested food particles) into the host (into tissues, into blood vessels), activating an immunological response. Intestinal epithelial tight junctions are another key players (proteins) keeping our intestinal barrier intact by functioning as a seal between neighboring gut cells. Disrupted epithelial tight junctions can be found in a leaky gut.

Regulation of gut permeability: what to blame for an increased intestinal permeability?

Besides genetics, environmental factors also play an important role in keeping our intestinal barrier intact with normally functioning permeability. Possible harmful factors include nutritional factors, pathogens, toxins, too clean/sterile environment (the hygiene hypothesis), too low microbial gut diversity with impaired microbial functioning (the lifestyle hypothesis), or endogenous factors (chronic inflammation/autoimmunity).

Intestinal permeability may be influenced by:

1. The gut microbiota - dysbiosis

The gut microbiota is involved in a number of processes, such as the production of vitamins and hormones, metabolism and absorption of nutrients, and protection against pathogenic organisms. There is constant fine-tuning between the host’s immune system and the gut microbiota to maintain an equilibrium-homeostasis state and promote health. The healthy gut microbiota stimulates the synthesis of protective mucus (mucus sugars) lining by the gut epithelial cells. Some bacteria regulate the mucus layers by using the mucus components as an energy source so there is no mucus overgrowth. There is a regulation at multiple levels between the gut microbiota and the intestinal barrier. If the microbial gut ecosystem is out of balance, leading to dysbiosis and/or increased activity of pathogens, it may in turn promote inflammation, altered intestinal permeability and gut barrier damage. For example, some pathogens such as Helicobacter pylori, Salmonella eterica serovar typhimur., Clostridium difficile, or Vibrio cholera were shown to disrupt the epithelial tight junctions, increasing the intestinal permeability.

2. Diet

Diet, apart from an individual’s genetic imprint and gut microbiota, may affect to a greater or lesser extent, the gut permeability. Some studies have shown that Vitamin A deficiency may compromise the intestinal lining. Additionally, Vitamin D deficiency may potentially have a similar effect. Short chain fatty acids (SCFA), such as butyrate, produced by the gut microbiota play an important role in intestinal barrier formation and maintenance. Individuals suffering from Irritable Bowel Disease (IBD) were shown to have intestinal permeability and barrier impairment that has been linked to the deficit of butyrate, produced by the gut microbiota. In addition, A1 casein present in dairy cow products may also contribute to the problem. Let’s not forget about the negative effect of the overconsumption of alcoholic beverages. Lectins present in legumes show affinity to intestinal mucosa, which make the mucosa porous and leaky. It has also been demonstrated that commonly used food additives increase intestinal permeability, potentially leading to the gut leakage.

Lets pay some attention to food additives:

Sugars  can be found in most processed foods. Glucose is an absorption enhancer and an increased gut permeability is required for its absorption. It has been shown that the presence of glucose affects the distribution of an intestinal barrier related protein (Caco-2), which may lead to the disruption of intestinal tight junctions and consequently to the intracellular leakage.

Salt – usually overconsumed, salt has been associated with strokes, hypertension, renal diseases and obesity. About 75% of sodium intake comes from manufactured foods, such as baked goods or cereals. Recent studies indicated that increased salt consumption enhances the intestinal permeability by disrupting the functioning of claudins (2 and 15) and proteins, which are the backbone component of the intestinal tight junctions.

Emulsifiers/surfactants there is plenty of these substances available and used in the food industry. The emulsifier market is growing worldwide. The list is long but commonly used emulsifiers include mono-and di-glycerides of fatty acids, sucrose esters of fatty acids, polyglycerols of fatty acids, lecithin, glycolipids, saponins, unsaturated and saturated/trans fatty acids. They are widely used in the bakery products, dairy, sauces, margarine, ice cream, beverages, chocolates and many other products. Many (synthetic) surfactants are shown to increase intestinal permeability. For example sucrose monoester fatty acids, which are widely used in the food industry – even in infant formula - have been shown to compromise the intestinal integrity of tight junctions.

Organic solvents - used to dissolve another substance. They need to be handled under special conditions as they are poisonous. Some commonly used organic solvents in the industry are benzene, xylene, toluene, acetone, hexane, ethanol, and some detergents. They are typically used in the process of extraction of active compounds and/or removal of unwanted substances, such as in oil production. Some are used as food additives. For example, alcohol and its metabolites were shown to breach the intestinal barrier.

Gluten – typically to be found in wheat derived products. Gliadin, one of gluten’s proteins, in known to increase the gut permeability and to contribute to intestinal damage.

Microbial transglutaminase – an enzyme of microbial origin commonly used in industry to simplify certain manufacturing processes related with economic savings. It is used to improve the texture and appearance of meat, fish, dairy products, bakery products, and sweet products, among many others. Scientists are alarmed that microbial transglutaminase may increase intestinal permeability by affecting/cross-linking certain amino acids and/or proteins.

Nanoparticles – Particles at dimensions between 1 and 100 nm (nanoemulsions). These nanoemulsions are applied in the food industry in order to protect, encapsulate, and enhance delivery of bioactive components such as lipids, flavors, vitamins, preservatives, and nutraceuticals. Nanoparticles increase the intestinal permeability by facilitating the transport of molecules and drugs through the gut lining. Chitosan is a common component of nanoparticles with the shown ability to enhance permeability and intestinal absorption of active agents.

There are other compounds shown to increase the intestinal permeability, such as L-alanine, tryptophan, and epigallocatechin galat (polyphenol in green tea).

3. Use of medication such as non-steroidal drugs like aspirin, birth control pills, steroid drugs, chemotherapy

4. Chronic Stress

Where does a leaky gut take us to: Diseases on the rise

Over the past decades there has been an increasing incidence of autoimmune and other diseases. Many of them have been associated with increased intestinal permeability and a leaky gut. The entry of foreign antigens (toxins, microorganisms, gluten, etc) to the inner host, due to the increased intestinal permeability and leakage, can, in susceptible individuals, initiate immunological-autoimmunological responses.

How do I heal a leaky gut?

  • Eliminate (if known) foods (gluten, sugar, dairy products, GMO products etc) and factors (stress, toxins, pesticides) causing a leaky gut
  • Drink Bone Broth = proline, glycine and collagen will soothe and help repair the gut lining
  • Eat healthy and raw foods (vegetables) = Feed yourself and your gut microorganisms nutritious foods
  • Reduce sugar consumption (consider a low FODMAP diet) and processed fat consumption = avoid energy-dense western diet
  • Avoid processed foods. They contain a lot of food additives that may compromise the gut lining and barrier and compromise your bodies’ acid-alkaline balance
  • Eat probiotic (kefir, sauerkraut, kimchi) and prebiotic (leak, chicory root, onions, banana) rich foods
  • Consider L-Glutamine supplementation
  • Consider probiotic supplements (with Lactobacillus plantarum, Lactobacillus rhamnosus GG, Lactobacillus casei, Lactobacillus salivarius, E. coli Nissle 1917)
  • Add anti-inflammatory foods (Omega-3 rich) to your menu
  • Consider Zinc supplementation (zinc carnosine)
  • Consider Quercetin supplementation
  • Consider Vitamin A supplementation

How do I know if I have a leaky gut? Are there any lab tests?

Suffering from any of above mentioned diseases may indicate you have an impaired intestinal permeability and an impaired intestinal barrier. Discomfort related to food sensitivities, cramps, gas, bloating, and/or aches and pains may also be a sign.

Sources:

“Intestinal permeability – a new target for disease prevention and therapy”. Bischoff at el., BMC Gastroenterology 2014, 14:189

“Changes in intestinal tight junction permeability associated with industrial food additives explain the rising incidence of autoimmune disease”. Lerner & Matthias, Autoimmunity Reviews 2015, 479-489.

“Intestinal permeability regulation by tight junction: implication on inflammatory bowel diseases”. Sung Hee Lee, Intest Res 2015; 13 (1): 11-18.

Diseases, Microbiome and gut health
Jul
27
Early antibiotic use may impact health later in life

Antibiotics, once being the best intervention ever, now lead to antimicrobial resistance, posing one of the greatest threats to human health

Antibiotic dilemma

My first experience with an antibiotic dilemma was directly after my first daughter was born. Three hours after giving birth, we were heading home from the hospital, with my daughter in a newborn car seat. About 15 minutes later, I noticed she turned pale and I became suspicious. We returned immediately to the hospital, where the medical team discovered she had a respiratory insufficiency. No one knew the cause of it. She had no fever but doctors, following our approval, gave her antibiotics just in case it was an infection. We were told that if it turned out to be an infection, not giving her antibiotics would risk her life. That was a clear message which made us decide to go for antibiotics. Nobody, however, warned us about the potential consequences of (unnecessary) antibiotic exposure at such a young age.

Eventually, it turned out that it wasn’t an infection. The microbiological tests came back negative. Doctors found no cause of a respiratory insufficiency. I have, however, a theory that placing her in a car seat (bended body, bended head) was a trigger leading to breathing difficulties. The antibiotic she was given at this very critical lifetime might have compromised her gut microbiome establishment and her immune system development, and hence could be the colic as the first sign of it and later on frequent sicknesses. Around her 2nd birthday she had 3 antibiotic courses, one for impetigo and two for ear infections. Each time she was prescribed an antibiotic, I was hesitant to give it to her, wondering what the price she will pay for it in the future. I can imagine many parents face similar situations. Often out of fear and to feel like we are in control, we allow our children to be given antibiotics. In the short term, there is usually an improvement, which makes us believe that the antibiotics were the right choice. Antibiotics are often the only way but we still need to be careful when subjecting our children to antibiotics.

Antibiotics have served their purpose in fighting bacterial infections, there is no doubt about that. Most bacterial infections, causing deaths decades ago, are under control thanks to antibiotics. Antibiotics became a miracle drug and are often generously prescribed. But do we know the long-term effects of antibiotic use? Decades ago, people were dying because of infections. Nowadays they are dying because of non-communicable diseases. Could there be a link between the use of antibiotics and the diseases we currently face? According to a review that just appeared in Cell Host & Microbe scientific journal, the use of antibiotics, especially at early age, may lead to microbial imbalances. These imbalances may contribute to dysbiosis associated diseases, such as obesity, autoimmune diseases and infectious diseases, apart from the already known drug-related adverse events and growing antibiotic resistance.

I want to increase an awareness about their potential long-term effects when administered early in life, based on the review mentioned above.

Children are prescribed antibiotics more than any other prescription drugs

It has been suggested that up to one third of antibiotics are unnecessarily prescribed. I find it alarming and worrisome.

The World Health Organization emphasizes that antibiotic resistance is one of the three greatest threats to human health.

The 3 most alarming effects of an inappropriate use of antibiotics include:

  • Antibiotic resistance (the prevalence of antibiotic resistance genes increases worldwide and infections caused by resistant bacterial strains lead to increased morbidity, mortality and increased healthcare costs)
  • Antibiotic-related side effects (about 20% of all emergency department visits in the US are because of antimicrobial-related adverse events)
  • Dysbiosis referring to microbial imbalance (recent findings indicate there is an association between exposure to antibiotics at early age and dysbiosis related diseases such as obesity, diabetes, or asthma)

The presence of microorganisms early in life is essential in the neurological, immunological and metabolic development of a child

The early exposure to certain factors - such as to microorganisms, to dietary antigens, hormones, or growth factors - is prerequisite for the development of the immune system, the establishment of healthy digestive function, gut motility, immune tolerance to foods and various antigens, and defense against pathogens. For more information please go to my blog on "Gut microbes in infancy".

This is the time when organs and systems are being developed and trained so they can serve throughout life. If perturbation occurs at early age (especially the first 6 months of life), such as exposure to antibiotics, it may have distinct and long-term consequences.

 The possible effects-scenarios of early (0-6 months of age) exposure to antibiotics:

  • Antibiotics temporarily decrease the bacterial diversity, without affecting the species critical for immune development so the immune system develops normally. On the other hand, the microbial community does not recover completely post-antibiotics and it gains a new state with altered microbial composition and altered metabolic capabilities. As a result, it could lead to obesity. From the animal studies we know that the exposure to sub-therapeutic levels of antibiotics increases adiposity, or fat accumulation. This is one of the reasons why livestock have been fed low doses of antibiotics to increase their body mass. 
  • Antibiotics eliminate the key bacterial species during a critical window of the immune system development, leading to its maturation impairment. During the post-antibiotic recovery the key members of the gut microbiome return to occupy their niches and the microbiome reaches a state of “stasis.” The returned key species let the immune system develop further. However, the immune system remains impaired. As a consequence, the immunity is compromised and may lead to allergy, atopic disorders, and autoimmune diseases. A number of studies associate early antibiotic use, especially multiple courses of broad-spectrum antibiotics, with an increased risk of allergy and atopic disorders. According to a current hypothesis, gut dysbiosis caused by the loss of key bacterial players and overgrowth of pathogens may contribute to the development of allergy, atopic diseases, and autoimmune diseases. The genetic factor is known to be involved in the etiology of autoimmune diseases. However, scientists indicate that the gut microbiome may be as well an important player. There are results to suggest that early exposure to multiple antibiotic courses may increase the risk of juvenile rheumatoid arthritis and inflammatory bowel syndrome. In addition, animal studies showed that exposure to antibiotics led to alterations in the gut microbiome and the loss of keystone species, eventually affecting the immune system.
  • Antibiotics decrease the microbial diversity within the gut and at the same time create a niche for pathogens. The gut is “on fire”: the gut epithelium is inflamed, the pathogens begin to thrive, predisposing to chronic infections. Thus, exposure to antibiotics may cause an increased vulnerability to infections during the post-antibiotic recovery period. Studies with pre-term infants suffering from necrotizing enterocolitis associated this condition with prior-antibiotic use. Clostridium difficile infection in adults is a classic example of the post-antibiotic loss of microbial gut diversity and subsequent pathogenic colonization. It is also known that antibiotic-induced dysbiosis increases the risk of fungus infection, such as Candida albicans. In addition, the post-antibiotic effect has been linked with impaired immunity against the influenza virus.

Summing-up, there are four post-antibiotic types of dysbiosis proposed currently: loss of keystone species, loss of microbial diversity, alterations in metabolic capacity, and blooms of pathogens.

Hopefully, these findings will fuel further research on the post-antibiotic health consequences and will improve antibiotic prescription protocols. For example, doctors should select narrow-spectrum antibiotics to target only designated bacteria based on proper diagnostics.

Lastly, I would like to encourage everyone to read an inspiring book of Dr. Martin Blaser: Missing microbes – how the overuse of antibiotics is fueling our modern plagues. The author will make you rethink the current concept of fighting infections, will make you cherish and appreciate your microbiome and will make you think twice before giving your child antibiotics.

Microbiome and gut health
Jun
03
Right from the start: gut microbes in infancy

Bringing my daughters into this world was quite an unforgettable experience. I had a lot questions and uncertainties prior to giving a birth for the first time so I took birthing workshops, pregnancy yoga classes, and a lactation workshop to prepare myself better for what was going to happen. These preparations certainly gave me some degree of confidence, yet looking back I feel like there was still something missing. Everybody kept elaborately telling how the baby goes through the birth canal and how to push, but nobody mentioned anything about the importance of the surrounding microorganisms in the first minutes, days, weeks of a newborn’s life.

As governed by Mother Nature, babies acquire their first significant dose of microorganisms from their mothers during the birth. Bacteria colonize the newborn’s every surface, including their skin and the mucosal membranes of the digestive tract, respiratory tract and urogenital tract.  This population of microorganisms (microbiota) remains with us from birth to death, helping us maintain balance by constantly responding and adjusting to internal and external factors. Learning more about human microbiome, in infancy and through the lifespan, can help answer some fundamental questions, such as its importance in our health and disease.

Interestingly, the most recent findings contradict the common belief that the healthy maternal womb is a sterile environment, and that the fetus is not colonized with bacteria until the birth. Thus, the new studies have found commensal bacterial species in placenta, amniotic fluid and fetal meconium, suggesting that the microbial acquisition actually happens before the birth. During the 3rd trimester of pregnancy, as the fetus matures it swallows more amniotic fluid, and this is probably the first manner of contracting microbes. In support of this hypothesis, the results of one study found shared bacterial species from the amniotic fluid in the meconium of neonates. The first microbes occupying the newborn’s body create a complex and life-long relationship with the newborn. The early-life gut microbes are believed to stimulate the development of the immune system, the establishment of healthy digestive function, gut motility, immune tolerance to foods and various antigens, and defense against pathogens. As the baby grows, it is constantly exposed to various microbes through contact with people, new foods, animals, exposure to medicines, and all these experiences contribute to a unique and individual microbial finger print for each and every human. The first 3 years of life are critical for the neurological, immunological and metabolic development of a child, as well as for the establishment of the microbial gut microbiota. This is the time when the foundation is laid that will play a role in our health in the future. At the age of about 3 years, the gut microbiome resembles an adult microbiome.

What if the baby is born by C-section?

The C-section originates from Roman times, when it was introduced to save the baby’s life, the mothers always died. Nowadays, the C-section procedure saves the mothers’ lives as well, but it has also become such a routine procedure that some mothers and/or physicians decide to deliver the baby this way out of convenience. Does the mode of baby delivery affect the infantile gut microbiota? It actually does, infants born vaginally colonize bacteria found in the maternal vagina, such as Lactobacillus and Prevotella. Whereas, C-section delivered newborns will be home for microbes found on the skin, typically including Staphylococcus, Clostridium, Propionobacterium, and Corynebacterium species. As a result, they have lower numbers of anaerobic (requiring no oxygen for growth) microorganisms of Bacteroides and Bifidobacterium commonly found in vaginally born infants. So as a result, we can see that having a C-section, to some extent, deprives babies of their naturally occurring, naturally evolved and selected vaginal microflora. So in the end, what is the price the infant will pay when born by a C-section? Well, there is still more research needed to provide clear answers, but I believe that it undoubtedly influences the individual’s gut microbiome, and therefore may have long-term consequences on gut function and even health. The microbial acquisition, in concert with other factors, within the first week of life sets a ground for the composition of the baby’s future gut microbiota. I appreciate that Dutch midwives and Dutch health care promote and encourage natural birthing, as this practice plays an extremely important role in preserving our precious microorganisms.

The breast milk influences infantile gut microbiota

It’s always been said that breast milk is the optimal choice. Indeed it is, as it is the most nutritious drink containing all what a newborn needs. Apart from containing carbohydrates, fatty acids, lactoferrin, vitamins, immunological mediators, and others, it also contains antimicrobial proteins and bacteria itself. Yes, babies get microbes through their mother’s milk. Healthy mothers with a balanced gut microbiota will transfer the friendly bacteria that colonize the neonatal intestines through their milk. So how do bacteria end up in maternal milk? It has been indicated that maternal gut bacteria travel to the mammary glands through the lymphatic and circular pathways, forming together with a mammary skin microbiota a main bacterial composition provided to a baby while breastfeeding.

Formula-fed infants, in comparison to breast-fed infants, receive a different combination of nutrients, carbohydrates and bacteria, leading to a different bacterial gut colonization and a different pattern of immunity development. As a result, healthy breast-fed babies have more intestinal colonization with Bifidobacteria than healthy formula-fed babies. The latter have broader bacterial scope, including Bifidobacteria, Bacteroidetes, Clostridia, Enterobacteria and Streptococci.

Premies and their gut microbes

Babies born pre-term are challenged in many ways when facing the new world and acquiring their bacterial partners. They are often born with underdeveloped organs and immune systems, and with a low birth weight. They are often being exposed to a number of medications to increase their survival chances and to help their organs to mature. It sets a tougher starting point for them in comparison to full-term born infants in general, and in terms of their microbiome maturation. I was born prematurely at about 36 weeks gestational age together with my twin sister, so it’s very interesting for me to know what happens when premies meet the microbes. It has been reported that pre-term babies have lower microbial gut diversity than full term babies, Bifidobacterium is less abundant, and there is an increased number of pathogenic strains. Bifidobacterium species are believed to be key players in the development of a healthy gut microbiota. The unfavorable combination of factors makes premies fragile and more vulnerable to all sorts of conditions such as life-threatening infections or serious diseases including necrotizing enterocolitis. The preterm gut microbiome reaches its adult-like pattern later than in the full term infants. Thankfully, the advances in medicine nowadays increase pre-term infants’ survival chances, while helping them to have normal lives in the future.

The infantile delicate gut microbiome, even in healthy full-term infants, is constantly exposed to many influences such as diet, environment, medications, and pathogens. These may in turn lead to changes in microbial composition, leading to imbalance – dysbiosis, and even have a profound effect on short- and long-term health. Hopefully, growing knowledge in the field will help us make better choices around the birth and developing healthy infantile microbiota for our children.

Microbiome and gut health
May
11
Gut feelings - gut microbes contribute to our MOOD and BEHAVIOR

It seems weird to think that our gut microorganisms may have something to do with our mood and our behavior. We know now that they play a role in many diseases, but do they also have a say in how we feel? Actually, yes, they do! There is a growing number of publications on the subject and I was prompted to write this piece after reading a recent (April 2015) article about the effect of probiotics on the activation of negative thoughts associated with sad moods. Please read on if you want to find out more about the results of this study.

In the human body, in nature, nearly everywhere, microorganisms form complex and sophisticated communities of cells that communicate with each other by means of a special language, a sort of microbial language. They produce so called “language" molecules that they can sense and respond to accordingly. During my doctoral research, one of my study topics was to look at the signaling (“language”) molecules of Pseudomonas aeruginosa, an opportunistic human pathogen. It uses the signaling molecules to communicate with other bacteria of the same species or other species, to switch on and switch off certain genes/functions. The great spectrum of molecules produced by bacteria plays various functions within the bacterial community itself and within their host, affecting thus other bacteria and affecting their host, for example a human body. There are up to 1000 microbial species in our gut and the molecules produced by these microorganisms help them to occupy certain intestinal niches (neighborhoods), to compete with other microorganisms for food, to communicate, to establish their role within the community or to become virulent (pathogenic). These molecules may comprise signaling molecules (“language” molecules), virulence molecules (making them virulent), various metabolites, neurotransmitters (they transmit the signals within the nervous system, such as serotonin, dopamine, norepinephrine), and many more. Microbial molecules may – via multiple routes – influence communication with our brain and even influence brain function. This gut-microbial pathway of communication is called a Brain-Gut-Microbiota axis.

How do gut microbes shape our behavior?

It has been suggested that without our microbial gut friends, we wouldn’t be able to develop our brain properly, and that our social abilities are also influenced by the gut microbiota. Molecules produced by bacteria can influence our mood and behavior as shown in studies with rodents. For example, germ-free (without any bacteria) mice are socially impaired with autistic-like behavior, they are anxious and they also have significant cognitive deficits in memorizing, recognizing, and learning. Interestingly, other studies showed that behavioral traits can be influenced by microbial transfer between species. For example, the transfer of gut microbiota from anxious mice to normal mice led the development of anxious behavior by normal mice. It has also been indicated that the microbial gut composition at early age plays a role in the development of an appropriate stress response later in life.

As mentioned above, scientists have identified a number of molecules (such as serotonin or corticosterone) that may be involved in neural signaling, but there is still more research needed to unravel the entire puzzle. One piece of the puzzle points to 95% of a neurotransmitter serotonin (commonly considered to contribute to the feeling of happiness and wellbeing) modulating the gastrointestinal tract motility and mood is being produced by microbial organisms present in the gut.

Microbes and social interactions

Recent findings indicate that the gut microbiota plays a role in Autism Spectrum Disorders (ASDs). ASDs refer to neurodevelopmental disorders with impaired social and communication skills. The presence of autistic symptoms has been associated with overall lower microbial gut diversity. The lower microbial diversity could be a result of the westernization of our lifestyles, also the use of antibiotics. Gastrointestinal complaints, such as constipation or diarrhea, are very common among autistic children. Moreover, autistic behavior has also been associated with certain metabolites produced by the gut microbiota. In autistic-like mice, the presence of a number of bacterial gut metabolites affecting neuro-behavior have been higher than in normal mice.

Could Probiotics affect our mood or help in dealing with depression?

Many questions are being asked nowadays as to the effectiveness of probiotics, and many studies are being conducted to answer these questions. The preliminary results from rodent and pre-clinical studies shed some light that probiotics indeed may have a therapeutic effect in regulating stress levels, anxiety or depression.

A probiotic strain Bifidobacterium infantis 35624 was found to have an antidepressant effect in adult rats with depressive-like behavior. This probiotic effect was comparable to the effect of the commercial antidepressant citalopram. Likewise, probiotic Lactobacillus rhamnosus JB-1 reduced depressive-like behavior and anxiety in otherwise healthy mice. The results of another animal study showed that ingestion of Bifidobacterium breve NCIMB702258 led to the increase in two (AA, DHA) fatty acids within the brain, which could be clinically important in cognitive functions such as learning and memorizing. Moreover, the treatment of autistic-like mice with Bacteroides fragilis resulted in improved communication, improved sensorimotor behaviors and decreased anxiety.

Also encouraging results, though very limited yet, come from human studies. Participants of one study who ingested a probiotic product containing Lactobacillus helveticus R0052 and Bifodobacterium longum R0175, for one month, were less psychologically distressed than the control group. Another study showed that daily intake of Lactobacillus casei Shirota for 2 months resulted in reduced anxiety in patients with chronic fatigue syndrome. Moreover, consumption of a fermented milk product containing 4 probiotic strains* by healthy females, for 4 weeks, showed altered activity in emotional brain centers as determined by the functional magnetic resonance brain imaging. Interestingly, consumption of prebiotic (soluble fiber – oligosaccharide - that stimulates the growth and/or activity of friendly gut bacteria) by healthy individuals was associated with lower levels of salivary cortisol (released in stress) upon waking and improved attention to positive versus negative stimuli based on an emotionally-oriented task.

Probiotics in the pursuit of happiness?

 As mentioned in the beginning, Dutch scientists have studied the effect of probiotics on the development of sad moods. In this clinical study, 20 healthy participants were given a multispecies** probiotic cocktail for a period of 4 weeks, to investigate its effect on cognitive reactivity (vulnerability marker of depression) to sad moods. A control group of 20 healthy participants received a placebo (no probiotic strains) for the same period of time. Enrolled participants had no psychiatric or neurological disorders, and no depression.

Based on questionnaires completed by all participants, researchers found that the probiotic-participants had, in comparison to the placebo-participants, decreased overall reactivity to depression, aggressive and ruminative thoughts. This results indicate that probiotics may have a potential to reduce negative thinking associated with sad mood. This study did not look, however, at the diet regimen of its participants and the dietary element may be an important factor influencing the findings of the study. The study results certainly bring to the table a promising alternative in the management of neurological and psychological conditions, but further research is required before we start taking probiotics in prevention of sadness or the treatment of depression. It is important to keep in mind that not all probiotics are the same and different probiotic strains may have different effect on their host.

Low diversity within the gut microorganisms, exposure to antibiotics and chemicals, gut dysbiosis, a poor diet, or genetic factors can affect molecules (type and quantities) being produced by our gut microorganisms. These molecules, just as certain foods or drugs, may in turn facilitate certain moods and/or behaviors. The gut microbiota influences our brain chemistry and consequently our behavior but we shouldn’t blame these guys solely if we feel sad or are depressed. It is much more complex than we realize!

*Bifidobacterium animalis lactis, Streptococcus thermophilus, Lactobacillus bulgaricus, and Lactococcus lactis lactis

**Bifidobacterium bifidum W23, Bifidobacterium lactis W52, Lactobacillus acidophilus W37, Lactobacillus brevis W63, Lactobacillus casei W56, Lactobacillus salivarius W24, and Lactococcus lactis W19 & W58

Microbiome and gut health
Apr
16
Gut Microbiota – an unappreciated organ

Microbiota – Behind the scenes

The microorganisms within our intestines form a complex community called microbiota. The gut microbiota occupy intestinal spaces. Microbiota, sometimes called microflora, is a community of microorganisms to be found either on the surface of the body, or in its different cavities: the skin, mouth, ears, vagina and gastrointestinal tract.

Our present day knowledge of microbiota began with the pioneering work of Russian scientist Élie Metchnikoff, winner of the 1908 Nobel Prize, who explored the ageing process and intestinal bacteria. It wasn’t until the 1970s that scientists began to publish about the importance of these intestinal inhabitants to the wellbeing of the human body.

Our microbiota comprises of commensal (native) and transitional (just passing through) microorganisms. Transitional organisms typically include non-fermenting gram-negative-bacili from the environment, contracted through food and drinks. They travel through our digestive system mostly harmlessly, and are eliminated with feces.

Microorganisms can be beneficial, opportunistic (potentially harmful) or pathogenic. Commensal beneficial microorganisms contribute to our normal, healthy flora, and are commonly referred to as indigenous friendly bacteria. Some commonly known microbes include Bifidobacterium, Eubacterium and Lactobacillus. Opportunistic microorganisms, typically non-pathogenic, will keep quiet in a healthy host with a healthy immune system and well established gut microbiome, but may strike (become pathogenic) causing health issues in individuals with compromised immune systems, causing gut dysbiosis. Common opportunists include Bacteroides, Peptococci, Staphylococci, Streptococci, Bacilli, Clostridia, Yeast, Enterobacteria and more. Common exogenous pathogenic microbes, entering the body via contaminated water or foods, include rotavirus, Salmonella typhimurium and some Escherichia coli strains.

Indigested probiotic organisms are transient; some strains may colonise the gut temporarily, but will eventually be expelled a few days after their consumption.

How does it develop through life? How do we get all these microbes?

Until recently it was believed that our digestive tract is sterile until birth. Recent findings, however, indicate the presence of bacterial commensal species already in the fetal environment such as amniotic fluid, placenta, or meconium. But babies indeed acquire most bacteria during and after birth, bacteria occupy then the newborn’s skin and mucous membranes, including the digestive system. Babies will, in no time, contract various microbes. The microbial fingerprint of a baby is determined by many factors, including the method of delivery (vaginal or C-section), the environment during the birth (hospital or home), hygiene, the health status of the mother and her own microbiota, the baby’s health status (including genetic factors) and the method of feeding. Once the baby is exposed to new foods, the number and diversity of gut microorganisms will change, and stabilize by around 3 years old, to resemble the adult microbiome. The exact composition of gut microbes is, however, unique to every individual.

How stable is our gut microbiota?

Our gut flora, the core bacteria, is relatively stable throughout our lifetime. However, there are many factors that will challenge, boost, change or disrupt our gut microbiota. Many of these factors are hard to avoid in westernized societies.

Potential dangers to the gut flora:

  • Drugs (antibiotics, non-steroidal anti-inflammatory drugs, steroid drugs, birth control pill, sleeping pills, heartburn pills, cytotoxic drugs, etc.)
  • Poor diet (consumption of processed food, excess sugar and processed carbohydrates, improper nutrient intake)
  • Exposure to chemicals and toxins
  • Disease (infectious diseases such as cholera, salmonella, some viral infections and chronic diseases such as diabetes, autoimmune diseases, neurological conditions, immunocompromised patients)
  • Stress
  • Other factors (surgery, chemotherapy, hormone therapy, radiotherapy, excessive alcohol consumption, lack of sleep etc.)

Some numbers to digest

Our gut is home to hundreds of trillions of microorganisms, between 500 and 1,000 different species. More than 99% are bacteria, and the remaining organisms consist mostly of archaea, fungi, protozoa and viruses. Together, they weigh about 1,5-2 kg, and the majority resides in the colon. There are about ten times more bacterial cells than human cells within you and the gut microbiome contains more than 3.3 million genes, about 150 times more than the human genome. About 60% of dry mass of human feces is of bacterial origin. Our intestine harbors about 70% of our immune cells, and more than a hundred million neurons connected with the brain.

What has gut microbiota got to do with the immune system?

Our immune system is constantly exposed to various stimuli and has to interpret and respond to them adequately. It protects us from harm by distinguishing between invaders (such as pathogens) and harmless stimuli. These white blood cells keep a close eye on events, especially in our intestines, as this is where the immune system can scrutinize most of the microbes and molecules entering our body from air, food and drinks. Most of the time, our immune system will watch and tolerate without raising the alarm, waiting until invaders show up. Once a harmful trigger is detected, the immune system will activate an appropriate cascade of responses.

So, what does our gut – our microbiota – have to do with the immune system? About 70% of the human immune system is located within the intestines, protecting us from pathogens and various antigens. If gut tissues are intact and healthy, bacteria and harmful particles will have limited chance of entering our blood flow and causing an immune response. On the other hand, if the gut is compromised it gives way to invaders, allowing undigested food to enter the tissues.

The intestinal lining serves as a physical barrier, interacting with the gut microorganisms which live in it. These friendly gut inhabitants positively regulate immunological responses within the gut and throughout the body, stimulating the immune system to help rather than harm us. That’s why microbiota is a key player in our health. A microbiological balance in the gut encourages a balance between inflammation and healing. If things get out of control (pathogens, poor diet, and disease) it leads to inflammation and disease. Long term gut dysbiosis and consequently immune imbalance may contribute to microbial infections, digestive problems, allergic disease, neurological complaints, and more.

Our digestive brain

Having a gut feeling suggests that the brain communicates with the gut and the gut communicates with the brain. This connection and communication allows you to feel butterflies in your stomach when you are nervous, causes stomach cramps and diarrhea when anxious, or makes you drunk after alcohol consumption. The two systems (nervous and digestive) communicate with each other, like two way traffic. The nervous system running through the digestive system is called the Enteric Nervous System (ENS). The vagus nerve connects the brain directly to the digestive system, which can actually function entirely on its own and is often therefore called the second brain. In the event of gut dysbiosis, the digestive system may become inflamed, which is then communicated to the brain and may result in certain behavioral changes or diseases such as depression, fatigue, anxiety or migraine. For example, people with irritable bowel syndrome or celiac disease will often have depression or anxiety.  Most autistic people have digestive complaints as well. Conversely, the brain will communicate certain behavioral changes to the gut, which in turn will respond, for example by altering gut flora and/or becoming inflamed. The neurotransmitters (serotonine, neurotensin, nitric oxide, substance P) working in our gut, also work in our brain.  So, we have a circuit: brain-gut-brain-gut.

Do we underestimate the role of microbes in our health?

Yes, we probably do, but there is a growing body of evidence that these little creatures, microbiota, carry out specific functions essential for human wellbeing. We have only now come to realize how complex and unappreciated their role and function in our lives is. Our gut microbiome coevolves with us and influences our metabolism, physiology, nutrition and immune function. The pool of these microorganisms functions much like an organ, by collectively performing important metabolic activities. We should certainly give them a high five for the amazing job they do within us!