18.7: Human Microbiome

Beneficial Microbes: The pharmacy in the gut

While some bacteria can cause disease, others play beneficial roles in human health. We have co-evolved with microbes in and on our body, with everyone having a unique set of microorganisms. The most abundant and well-studied microbiome is the gut microbiome. It has been estimated that the number of bacteria in the human gut may outnumber the body's cells by an order of magnitude. Thus, one may consider the gut microbiome as a multicellular organ similar in size to the liver. Indeed, it is sometimes referred to as our “forgotten organ”.

Generally, the microbiome within a given body habitat can be defined as the distribution of distinct types of microorganisms in terms of diversity and abundance. This microbial composition is strongly influenced by individual factors, including diet, age, lifestyle, ethnicity, and host health. Although no taxa are universally present among individuals, some microbial patterns exhibit broad prevalence. Most bacteria belong to the genera Bacteroides, Clostridium, Fusobacterium, Eubacterium, Ruminococcus, Peptococcus, Peptostreptococcus, and Bifidobacterium.

The evolution of the microbiome during life

Recent research suggests that early in-utero microbial exposure during pregnancy. Following birth, the newborn’s digestive tract is quickly colonized by microorganisms from the mother (vaginal, fecal, skin, breast milk, etc.) and the environment in which the delivery takes place. Following birth, the microbiome that enters and evolves in the infant's gut depends on several factors, with delivery mode and feeding regime (breastfeeding vs infant formula) being of prime importance in the early days and weeks of life. By the ages of 2 to 3 years, the microbiome becomes essentially established, reaches a steady state, and remains relatively stable throughout life. However, the gut microbiome continuously changes in response to daily variations in diet, lifestyle, age, and host physiological and immunological health.

Health benefits of the microbiome

Based on the current literature, the gut microbiome is known to contribute to a number of important functions in the host, including protective, immunomodulatory, metabolic, and trophic roles. These are promoted through several mechanisms. For example, members of the gut microbiome can produce anti-inflammatory factors, pain-relieving compounds, antioxidants, and vitamins to protect and nurture the body. Additionally, they may prevent attachment and action of harmful bacteria that can produce toxins, causing chronic disease. This close, specific contact with human cells, exchanging nutrients and metabolic waste products, makes symbiotic bacteria essentially a human organ.

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Gastrointestinal infection prevention

The indigenous intestinal microbiome serves as a line of defense against colonization by exogenous microbes such as Clostridium difficile and Helicobacter pylori, thereby assisting in competitive exclusion of pathogens and preventing potential invasion, a phenomenon termed colonization resistance. Indeed, antibiotic-associated diarrhea occurs when antibiotic treatment disrupts the natural balance of the gut microbiome, allowing harmful bacteria (e.g., Clostridium difficile) to proliferate. Oral probiotics may significantly reduce antibiotic-associated diarrhea.

Figure \(\PageIndex{1}\): Schematic representation of the cross-talk interaction of the indigenous microbiome and oral probiotics with the intestinal epithelium. The intestinal microbiome protects the mucosa from pathogen invasion. These probiotic bacteria may also allow beneficial effects through the release of nutrients (vitamins, SCFAs sugars) which are absorbed in the small intestine. Human microbes and probiotics would also interact with MALT macrophages and naive lymphocytes, thereby supporting a mucosal anti-inflammatory response. Beneficial Microbes: The pharmacy in the gut, Daniel M. Linares, Paul Ross, and Catherine Stanton CC-BY-NC

Immunomodulatory effects

Commensal bacteria can interact with the host immune system to modulate the host's response and help prevent disease. The complex interactions that may occur between ingested probiotic bacteria, commensals, and the mucosal surface are enabled by the mucosa-associated immune system, typically organized into MALT (Mucosal Associated Lymphoid Tissue, such as Peyer’s patches). This cross-talk enhances the cellular immune response, characterized by the activation of macrophages and antigen-specific cytotoxic T lymphocytes, and the release of various cytokines. Furthermore, some probiotics may be effective in preventing and/or alleviating allergies and autoimmune diseases, such as irritable bowel syndrome and inflammatory bowel diseases (Crohn’s disease and ulcerative colitis).

Nutritional benefits

The metabolic activity of the gut microbiome makes an important contribution to the nutritional status of the host, via its ability to synthesize certain vitamins and various bioactive metabolites, such as short-chain fatty acids (SCFA) that then become bioavailable to the host. It has been reported that consumption of yogurt containing Lactobacillus bulgaricus or Lactobacillus acidophilus can alleviate lactose intolerance during gastric passage by their enzyme lactase. However, the major metabolic function of the colonic microflora is the fermentation of nondigestible carbohydrates, which are key energy sources in the colon. These carbohydrates include large polysaccharides (e.g., resistant starches, pectins, and cellulose), some oligosaccharides that escape digestion, and unabsorbed sugars and alcohols. Other benefits of the gut microbiome on human health, such as its role in supporting the health of the reproductive tract, oral cavity, lungs, skin, and gut-brain axis, are currently under investigation.

Probiotic imbalance

When the normal composition of the microbiome is disrupted, there is a potential risk of disease. A decrease in microbiome diversity has been linked to cancer, asthma, Parkinson's, obesity, Alzheimer's, type-2 diabetes, cardiovascular disease, and possibly even autism in comparison to healthy subjects. Over-the-counter probiotics can help. To reach their target site (i.e., the gastrointestinal tract) alive, orally administered probiotics must resist stomach acid, bile, and digestive enzymes. Certain mechanisms of action (such as the delivery of certain enzymes to the intestine) may not require live cells to provide a physiologic benefit. Hence, a probiotic must contain as many live bacteria as claimed on the label. In addition, to survive the stomach and reach the intestine in optimal numbers, probiotic strains must adhere to the intestinal epithelium and/or mucus, persist, and multiply in the gut to maintain their metabolic activity and confer their probiotic properties.

How the food you eat affects your gut

The bacteria in our guts can break down food the body can’t digest, produce important nutrients, regulate the immune system, and protect against harmful germs. And while we can’t control all the factors that go into maintaining a healthy gut microbiome, we can manipulate the balance of our microbes by paying attention to what we eat. Shilpa Ravella shares the best foods for a healthy gut.

Reference

Linares, D.M., Ross, P., and Stanton, C. (2016). Beneficial Microbes: The pharmacy in the gut. Bioengineered, 7(1): 11-20. http://dx.doi.org/10.1080/21655979.2015.1126015