The microbiome: A tutorial

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The human gut is a complex organ that contains microbiota living in an elaborate microbial community with trillions of microbes dominated by several hundred species of bacteria, as well as other microorganisms such as archaeabacteria, viruses, fungi and bacteriophages (viruses that affect bacteria). 

These microbes have evolved over hundreds of thousands of years to adapt to the human gut and diet, and exist in a complex community involving a large number of interactions. Beneficial bacteria provide many health benefits, but some microbes or combinations of microbes can contribute to disease or cause many health disorders in the gut, brain and body. 

The microbiome at birth and through infancy 

The human gut microbiome is primarily colonized at birth, and infants inherit a portion of their microbiome from their mother. Some of the microbiome is acquired from passage through the vaginal canal during birth, but some is also from the mother’s fecal bacteria – birth is a messy process! Birth by Caesarian section prevents natural exposure to the mother’s vaginal and gut microbiome, and altered dynamics of microbial colonization of the newborn intestine may increase risk of infections and impact the development of the immune system. 

One of the more important factors in the early establishment of a healthy microbiome is breastfeeding. The fourth-largest component of human breastmilk is human milk oligosaccharides (HMOs). These HMOs cannot be digested by the human infant, but certain bacteria such as Bifidobacterium longum subsp. infantis can digest HMOs, allowing them to outcompete other bacteria and become the primary bacteria in the breastfed infant gut. Once an infant is weaned, B. infantis is gradually replaced by other bacteria that are generally beneficial. 

Many baby formulas now include some HMOs, a testament to the importance of this bacterium. However, decreased abundance of B. infantis has been observed recently, especially in industrialized societies, likely due in part to antibiotic usage. 

Research studies have suggested that providing B. infantis to human infants during breastfeeding has many beneficial effects on their health, and research is ongoing to identify optimal strains. 

Factors affecting gut microbiota  

Once a standard diet is consumed after weaning, the human gut microbiome is relatively stable between early childhood through adulthood. Gut bacteria are affected every day by the foods people eat, which provide part of the nutrient flow to microbes. The abundances of different bacteria are modulated according to one’s diet, and eating diverse foods contributes to increasing bacterial diversity. 

Antibiotics have a major effect on temporarily reducing gut bacterial numbers and abundance, sometimes resulting in gastrointestinal (GI) issues. The introduction of improved hygiene over the last 150 years (toilets, soaps, etc.) has led to less exposure to one another’s gut microbiota and other host microbiomes. The combination of antibiotics, increased hygiene and poor diets with low fiber have contributed to a decrease in the diversity of gut bacteria and a decline in gut health. 

Disease 

Disrupting the balance of gut microbiota is now known to contribute to a wide range of diseases. Moreover, this disruption can lead to overgrowth of pathogens, many of which produce toxins that can affect not only the gut but can travel throughout the body and affect the brain, heart, kidneys, liver and the rest of the body. 

Bacterial infections of the gut are becoming numerous. C. difficile infections, which result as a direct consequence of antibiotic usage, cause severe diarrhea that affects hundreds of thousands of Americans each year and kills tens of thousands, according to the Centers for Disease Control and Prevention. Altered composition of gut microbes is thought to be one of the major drivers of inflammatory bowel disease (includes ulcerative colitis and Crohn’s disease), which affects over 3 million U.S. adults, per the CDC. 

Growing evidence also suggests gut bacteria contribute to many other health disorders beyond the intestines, including gut-brain connection related disorders. People with Parkinson’s disease often develop constipation 20 years prior to the onset of Parkinson’s symptoms. 

Mood disorders such as anxiety, depression, bipolar disorder and obsessive-compulsive disorder have been correlated with certain bacteria. More than 40 studies have demonstrated differences in gut microbial composition (bacteria and yeast/fungi population) in children with autism, with gut disorders almost always beginning in infancy and the severity of autism correlating strongly with the severity of gut disorders. 

Prebiotics 

Dietary prebiotics are nutrients that are consumed by gut microbes. These are typically fiber compounds that the enzymes produced by humans cannot digest. However, specific commensal bacteria such as Bifidobacterium, Lactobacillus, Prevotella and Faecalibacterium can consume fiber and produce short-chain fatty acids (SCFAs) and other beneficial molecules. 

Common prebiotic supplements include beta-glucan (from oats), inulin (from chicory root) and fructans, as well as starches from grains and beans. A limitation of most prebiotics is that they provide nutrition for both beneficial and pathogenic bacteria. Another limitation is that some prebiotics of limited chemical diversity (GOS [galactooligosaccharides], inulin, XOS [xylooligosaccharides] and arabinoxylan [oligosaccharides]) can decrease bacterial diversity because they induce blooms of some taxa that outcompete others, whereas other more diverse prebiotics (corn fiber and polydextrose) increase diversity. 

Probiotics 

Probiotics are live microorganisms that benefit health. While it is conceivable that some probiotics could be used to treat, mitigate or prevent actual diseases, such claims would lead to a regulatory drug classification and require rigorous clinical trials to demonstrate efficacy. No probiotics currently on the market have satisfied the requirements to be classified as a drug. 

The American Gastroenterological Association has done a rigorous review and published guidelines on the use of probiotics for multiple common indications, and in general more research is needed for most indications. The majority of probiotics are sold as dietary supplements. These products typically contain from one to 10 species of bacteria (typically L. acidophilus, L. plantarum, L. rhamnosus, Bifidobacterium breve, B. lactis, B. longum and Streptococcus thermophilus, either alone or in combination). Only a limited number of bacterial species are listed as GRAS (generally recognized as safe) and do not require premarket review and approval by FDA. 

Some of the bacterial strains commonly used as probiotics are related to bacteria found in the human gut, although their laboratory culture conditions may have led to altered ability to interact with the human host. Other probiotic bacteria were originally selected for their ability to ferment foods for preservation and never had much intrinsic ability to interact with the host. 

It is important to recognize that none of the available probiotic products can restore a gut microbiota decimated by antibiotics. (Two strains, LGG and Saccharomyces boulardii, are recommended to prevent antibiotic-associated diarrhea.) In fact, some data indicate that such products can even interfere with post-antibiotic microbiome recovery. 

Postbiotics 

Postbiotics refer to products of microbial metabolism. The gut microbes constitute a major metabolic organ in the body, which is revealed by major differences in the profile of chemicals circulating in germ-free versus conventionally raised animals. Ongoing research is moving toward formulating some of these microbial metabolites to benefit health or treat diseases. 

Interestingly, some of the beneficial effects of fermented foods may be driven by postbiotics. 

Assessing the microbiome 

Recent improvements in gene sequencing have revolutionized understanding of the microbiome. Previously, culture methods were used to assess gut bacteria, but only a small percentage of bacteria can be cultured and identified. Gene sequencing now allows identification of bacteria down to the species or even strain level, making it possible to identify a large percentage of the microbiota present in the human gut. 

However, the understanding of that data is still limited. No good definition of a “healthy” microbiome exists — it can vary widely depending on a person’s diet and their indigenous bacteria and those they are exposed to. High levels of specific pathogens can clearly indicate a bacterial infection, but often disease-associated microbiota is complex. More research is needed to be able to use microbiome assessments as a diagnostic tool for human health and disease for most cases. 

The microbial community in the gut plays an essential role in health and disease. It provides vital and essential nutrients, prevents pathogen growth, and instructs and regulates the immune system. Additionally, emerging research suggests that gut microbes are not only linked to gut-associated diseases but also to brain disorders such as autism and Parkinson’s, mental health issues, cancers and diseases affecting the liver, kidneys and metabolism. Microbial-based treatments such as prebiotics, probiotics and microbiota transplant are promising methods to treat many gut and gut-brain disorders.