The Human Microbiome: Unlocking the Key to Health

What is the microbiome?

The word microbiome  describes the trillions of viruses, fungi, and bacteria that live on or within the human body in various habitats such as the skin, mouth, colon and vagina.  Each site has characteristics, including pH, water and oxygen content, temperature, and chemical metabolites, that favor certain bacteria over others.  Our normal flora can cause disease particularly if they are introduced into a different environment, such as from aspiration, surgery  or trauma.  Among these conditions represent the most common cases seen by an infectious diseases physician, such as pneumonia, surgical site infection, diverticular abscess, dental abscess, and urinary tract infections.  However, most of the times, our microbiome is either harmless, a state known as commensalism (+ for bacteria, 0 for host)  or even beneficial and important to human health, a relationship known as mutualism (+ for both).

Our bodies are actually a hybrid of human cells and bacterial cells.  In fact, we are more bacteria than human: 40 trillion bacterial cells compared to 30 trillion human cells, greater than 80% are red blood cells. Bacterial genes probably outnumber our human genes by 150 times.  Together our microbiome weighs between two and six pounds – about as much as an organ like the brain. 

Now that you have gotten a grasp of the scale of the microbiome, it is not a big leap to speculate that likely humans have evolved to accommodate this microbial relationship.  Microbes undoubtedly existed in the environment way before larger animals.  Our usual microbiome, although by no means static, is acquired from our first contacts with the environment, including the birth canal, the skin of the breast/hands of our mother, and later food.  The microbes in our gut may have been the key to the development of our gut immune system, which in an infant is at first impaired. since the gut is an entry point of the environment in the food ingested and is one of the immune system’s most active sites (70-80% of immune cells).  Stepping back a little, I will provide a broad summary of the gut microbiome.

What is the gut microbiome?  How do gut bacteria affect the digestive tract?

The  “gut microbiome” describes those microorganisms that live mostly within the large intestine, or colon.  It is the environment that is the most populous of bacteria within our bodies.  Within the gut, there may be more than 1,000 different species of bacteria (even closer to 35,000! species).  The majority of bacteria thrive without oxygen, and are known as obligate anaerobes.  Scientists are only able to isolate 10-25% of the microbiota with culture techniques.  Instead they rely on more specific DNA testing (e.g. 16S ribosome).  Bacteria represent 55% of the dry mass of stool, an estimated 4×10 exp 11 bacteria per gram of stool.

Gut bacteria begin to affect the human from at least the moment of birth – if not before. Babies are exposed to bacteria as they pass through the birth canal – but there’s some evidence that the fetus may pick up bacteria while still in utero (in the womb).  Researchers can determine this by culturing from the amniotic fluid the meconium, or the first movement of feces (Walker et. al, 2017).  Even how an infant is delivered affects the first bacteria that they will acquire:  with normal vaginal delivery, common vaginal flora, such as Prevotella and Lactobacillus; with a c-section, skin flora mainly Staphylococcus. Within the infant gut, Bifidobacteria are among the first bacteria to be found. These bacteria, along with factors such as antibiotic exposure, hygiene, geography and nutrition, will influence the development of the gut microbiome and the immune system.

As a child grows, the gut microbiome expands to include numerous microbial species, the top being Firmicutes and Bacteroides (both accounting for 3/4 of gut flora), Bifidobacteria and E. coli.  Near adolescence, a child’s microbiome reaches a peak of diversity before it reduces to what is seen in a normal, healthy adult (Heiman M, Greenway F, 2016).  Greater gut diversity has been associated with health and wellness, and less diversity is associated with disease states. Diet is the principle driver of microbiome diversity (discussed below). 

The bacteria housed in the gut can fulfill several benefits in the human host.  Certain bacteria, such as Bacteroides activate the gut immunity, causing the intestinal mucosa to express a gut antibody (secretory IgA).  Other bacteria, such as Bifidobacteria and Lactobacillus, provide competitive inhibition, keeping harmful bacteria from adhering to the intestinal wall and potentially causing an infection.  These bacteria reduce the risk of microbial or toxin translocation, or “leaky gut syndrome” (I will refer to it as microbial translocation).  In microbial translocation, bacteria and/or toxins (e.g. lipopolysaccharide from E. coli) gain entry into deeper tissues or even the portal bloodstream (which drains into the liver) through weaknesses in the intestinal cell barrier.  Microbial translocation may contribute to disease manifestations, such as liver abscess, local processes like diverticulitis and appendicitis, irritable bowel syndrome (IBS) and even endocarditis (There is a certain pathogen Streptococcus bovis that is associated with colon cancer). Some chronic diseases increase the risk of microbial translocation, including Crohn’s disease, celiac disease, lupus, cirrhosis, HIV, and diabetes.

colon-biopsy

colon-biopsy

Slide showing colonic architecture.  This patient was found to have local tuberculosis infection of the colon.

Taking probiotics that contain Lactobacilli and Bifidobacteria may relieve the symptoms of IBS in some people, but for many a diet replete in plant fiber and with reduced simple sugars and processed foods is often useful.  Fiber provides a number of benefits, including regulation of stools and some benefit in preventing weight gain and reducing the risk of diabetes, cancer, and heart disease.  Some gut bacteria produce fatty-chain acids, which benefit gut health, by digesting fiber. 

What are some of the other effects of the gut microbiome?

An important function of the gut microbiome is the production of several vitamins, such as B vitamins (e.g. cobalamin (Vitamin b12) and Vitamin K, a clotting factor.  For this reason, people who are taking blood thinners like warfarin, may need to have their dose adjusted if they need to go on antibiotics (antibiotics kill bacteria – lead to less vitamin K and less clotting protection).

The gut microbiome can also affect the central nervous system and autonomic nervous system, sometimes referred to as the gut-brain axis. For example, some gut bacteria produce metabolites which are similar to neurotransmitters, chemicals that are used by our nervous system. One of these serotonin is produced almost entirely within the gut and exerts a positive effect on the mood.  Millions of nerves connect the gut to the brain, so the gut microbiome may also regulate the messages that those nerves send to the brain. Some researchers have found differences between the gut microbiomes of healthy people and those of people with psychological disorders. Such differences suggest that the gut microbiome may affect mental health. It is still unclear if diet and other lifestyle choices affected those differences.

The gut microbiome helps control how the body responds to an infection by communicating with the immune system, and those communications keep the immune system from attacking beneficial bacteria. As Vitamin A strengthens the immune system, the gut bacteria control the amount of active Vitamin A in the system to keep the immune system from becoming overactive. In 2018, researchers at Brown University found that inflammatory bowel disease was caused by disrupted communications between the gut microbiome and the immune system.

How does the gut microbiome affect the heart and circulatory system?
The gut microbiome may also affect the health of the heart. A 2015 study involving 1500 people found that gut bacteria affected cholesterol levels. More specifically, they affected the production of triglycerides and HDL, “good” cholesterol. The researchers also found that certain bacterial families were less common in people who were overweight or obese.

Some harmful bacteria can increase the risk of heart disease by producing a chemical called trimethylamine N-oxide (TMAO) that can cause blocked arteries and can thus lead to a stroke or heart attack. TMAO causes blocked arteries by increasing coagulation. Some bacteria produce TMAO by converting L-carnitine and choline, which are nutrients found in animal products like red meat, into TMAO.

Gut bacteria can also affect blood sugar levels. In 2015, researchers worked with 33 infants who were genetically predisposed to developing Type 1 diabetes. The scientists noted marked changes in the infants’ gut microbiomes right before they developed diabetes: The diversity of their gut microbiomes declined, and the number of harmful bacterial species increased.

Another 2015 study found that people who followed the exact same diets could have different blood sugar levels. The researchers speculated that the differences were due to variations within their gut microbiomes.

What is gut dysbiosis or bacterial overgrowth?
Gut dysbiosis, or bacterial overgrowth, represents an imbalance between beneficial and harmful bacteria, where selection pressures favor the growth of more harmful bacteria and less microbial diversity.  The multiple causes include behavior (alcohol, hygiene, etc), certain medications, some chronic disease, antibiotics, and significant stress.

Behavior.  Diet has a strong effect on microbiome.  In the infant, breast milk provides an advantage for the growth of Bifidobacterium, which is not as prevalent in infants fed formula.  In adults, an intake of higher fruit and vegetable fiber, even if done for a short period of time, results in greater diversity of gut bacteria.  A western diet, high in animal protein, sugar and starch and low in fibers leads to a predominance of Bacteroides. 

Unprotected sex, particularly anal-oral sex, can lead to gut dysbiosis simply by exposing the participants to harmful bacteria.  Other than sexually-transmitted diseases, transmission of Salmonella and Shigella has been associated with higher risk practices. 

Additionally, poor dental and oral hygiene causes an increase in numbers of certain bacteria to that grow in the mouth, such as Streptococci and Prevotella and with this can cause imbalance in the entire population.  

Medications.  The main medications involved that can lead to dysbiosis includes antibiotics, proton pump inhibitors, steroids and chemotherapy.  Antibiotics can selectively wipe out certain bacteria or have a more generalized action, depending on the spectrum of the effect.  The more broad-spectrum an antibiotic, the greater the risk for significant gut dysbiosis.  Antibiotics such as fluoroquinolones, clindamycin and cephalosporins are among the greatest risk factors for Clostridium difficile (C. diff), known for toxin-associated diarrhea and more severe colitis.  The resulting infection causes symptoms like abdominal pain, watery diarrhea, nausea, and fever.  Proton pump inhibitors, and to a lesser extent H2 blockers (zantac, pepcid, etc) reduce the acid that is produced by the parietal cells of the stomach.  Acid is an important defense to bacterial populations ingested in food or drink.  This type of medication has been associated with an increased risk of C. diff, traveler’s disease, and gut dysbiosis or bacterial overgrowth.  Prednisone and other anti-inflammatory modulate the immune system.  There is also an impairment of glucose synthesis, referred to as a diabetogenic effect.  This can lead to an increase in populations of yeast and other microbes.  Some chemotherapies affect white blood cell lines temporarily, the greatest immune being the gut, and can be a source of gut translocation and fever. 

Disease conditions.  Gut dysbiosis has co-associated with a variety of conditions including irritable bowel syndrome, diabetes, inflammatory bowel disease, obesity, Type 2 diabetes, rheumatoid arthritis, psoriasis and atopic eczema.  Whether a particular microbiome signature is found in a specific disease state (e.g. cancer) is the subject of research efforts.

Stress states.  Various states of stress increase the production of hormones such as epinephrine, norepinephrine and cortisol.  For instance, surgery leads to excess norepinephrine release, which has been associated with overgrowth of Pseudomonas aeruginosa in one study.  Psychological stressors, even short disruptions, could alter microbial populations as well, likely related to stress hormones.

How can you improve your gut microbiome?

  • Healthy, Diverse diet:  For example, eating fruits and vegetables, replete with fiber, will increase the diversity of the gut microbiome.  Consuming less simple sugars and processed carbohydrates will also help to maintain gut bacterial diversity.  Eating fiber-rich foods like fruit, beans, whole grains, and legumes can stimulate the growth of Bifidobacteria. Whole grains are also a good source of beneficial carbohydrates that can help control weight and reduce the risk of cancer and diabetes. Prebiotics are a type of fiber that stimulate the growth of beneficial bacteria. Good sources of prebiotics include apples, artichokes, asparagus, bananas, and oats.Fermented foods like yogurt and sauerkraut contain beneficial bacteria like Lactobacilli and can decrease the number of harmful bacteria in the gut.

          By contrast, people should avoid diets that are high in simple sugars, such as with              processed foods, sweets and sweet drinks.  Even using artificial sweeteners like                  aspartame can stimulate the growth of harmful bacteria like Enterobacteriaceae                that can raise blood sugar levels.

  • Take antibiotics judiciously, when you really have no other choice.  Remember that probably 50% of antibiotics that are prescribed in the outpatient setting are unnecessary.  In my experience, this mostly occurs in the setting of a viral syndrome (upper respiratory tract infection), rhinosinusitis, or a miscellaneous skin condition.  The shift in microbe flora can lead to yeast infections and other dysbiosis, including a risk of C. diff.
  • Good sleep, regular exercise and good coping are likely also help.

Summary:  The gut microbiome should be considered an important “organ” in your body.  The greatest effects of our microbiome are in modulating the immune system and aiding in nutrition and digestion.  Studies have suggested a healthy, diverse state of microbiome is necessary for health and lack of complexity has been co-associated with disease states.  When you eat – you eat for your microbes too!

Jandhyala SM, et al.  Role of the normal gut microbiota.  World J Gastroenterol.  2015 Aug 7; 21(29): 8787-8803.
Heiman ML, Greenway FL.  A healthy gastrointestinal microbiome is dependent on dietary diversity.  Molecular Metabolism.  2016.  5(5): 317-320.

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