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The Role of Gut Microbiota and Implications for IBD

by Judith Gorski PhD, October 17, 2017 at 09:00 AM

Over the past 10 years, scientists have discovered that changes in the composition of the gut microbiota play a pivotal role in human health. The gut is home to thousands of microorganisms each with its own critical role. Furthermore, the composition of the microbiota differs extensively along the digestive tract.

Development of Gut Microbiota Starts During and After Birth

The colonization of microorganisms in the gut begins during and after birth. Prior to birth, it is believed that the intestines of the fetus are sterile and contain very few microbes. However, during delivery the infant is exposed to milieu of microbes.

Interestingly, delivery by birth canal exposes the infant to a more enriched microbial environment unlike those infants delivered by cesarean section, whereby the latter have reduced microbial inhabitants in the gut, although by 6 months of age the differences no longer are detectable.

External and Internal Factors Affect Early Life Microbiota Changes

Throughout early life, as one would expect, there is a pendulum of changes parallel with a shift in feeding mode - from breast- or formula-feeding to weaning, and the introduction of solid food. During this time, the gut microbiota is influenced by both external and internal factors. External factors include the type of food eaten and composition of maternal microbiota. Internal factors may include intestinal pH and physiological factors, such as immune responses.

Considering the abundance of external and internal factors that influence the composition of the intestinal microbiota in the human gut, it is actually rather stable at the phylum level. The Bacteroidetes and Firmicutes are conserved in virtually all individuals, although the proportions may vary. It is at the level of bacterial species where the variation in the composition of interindividual microbial communities exist.

Gut Microbiota Have a Variety of Roles, Include Metabolism, Bile Biotransformation, and Amino Acid Synthesis

The role of gut bacteria is to produce a variety of vitamins, synthesize all essential and nonessential amino acids, and carry out biotransformation of bile. In addition, the microbiome provides biochemical pathways for the metabolism of non-digestible carbohydrates, a major source of energy in the colon. The result is energy and absorbable substrates for the host and a supply of energy and nutrients for bacterial growth and proliferation.

Gut Bacteria Also Involved in Immune Response

Gut bacteria are important in the early development of the gut-mucosal immune system. The cells of the intestinal epithelium counteract pathogens by signaling to the immune system through specific receptors that recognize specific molecules associated with bacteria. This leads to the production of a host’s immune response and the release of protective peptides, cytokines, and white blood cells.

Exposure to intestinal bacteria is also implicated in the prevention of allergy. Allergic infants and young children have been found to have a different composition of intestinal bacteria than those who do not develop allergies.

It is therefore hypothesized that the intestinal microbiota stimulates the immune system and trains it to respond proportionately to all antigens. An altered composition of intestinal microbiota in early life can lead to an inadequately trained immune system that can, and often does, overreact to antigens.

When the Gut Goes Wrong – Development of IBS and IBD

Inflammation, infection, immunity and genetic factors are thought to play roles in the development of irritable bowel syndrome (IBS) which affects approximately 10 to 20% of adults and adolescents worldwide. The variation in the gut microbiota along with these factors is associated with the low-grade intestinal inflammation associated with the syndrome.

In a healthy gut, the microbiota protects the intestines with either a direct bactericidal effect or can prevent pathogenic bacteria from adhering to the intestinal wall. Alteration in the composition of the normal microbiota and disturbed colonic fermentation in IBS patients may play an important role in development of IBS symptoms, with a significant, 2-fold increase in the ratio of Firmicutes to Bacteroidetes reported in IBS patients.

Gut Microbiota also Linked to Obesity Through Leptin Mutations

With a mutation in the leptin gene, obese mice were shown to have a significantly different microbiota compared with mice without the mutation providing early evidence that the gut microbiota is involved in obesity. Further investigation indicated, like that in IBS patients, that the ratio of Firmicutes to Bacteroidetes in the gut microbiota of obese mice was shifted in favor of Firmicutes.

In more recent human studies, researchers found that the composition of the gut microbiota was altered in obese when compared with normal-weight individuals and that the composition changed in response to changes in a host’s body weight.

A Pivotal Role in Human Health

Clearly the gut microbiota plays a pivotal role in human health. In the healthy state, the gut provides energy recovery, protection of a host from pathogen, and a host of other positive functions. In its “dysbiotic” state, the gut microbiota is becoming more and more recognized as an environmental factor that interacts with a host’s metabolism and has a role in pathological conditions, both systemic, obesity, and gut-related IBS and IBD.

Although it remains unclear the specific contributions this complex community of microbe’s influences, continued advancements in high-throughput DNA sequencing methods are rapidly expanding knowledge about the gut microbiome and its role in human health.

Further Reading on the Gut Microbiota:

Guarner and Malagelada. Gut flora in health and disease. Lancet. 2003;361(9356): 512–519.

Guinane and Cotter. Role of the gut microbiota in health and chronic gastrointestinal disease: understanding a hidden metabolic organ. Therap Adv Gastroenterol. 2013;6(4): 295–308.

Learn more on the microbiome and IBD


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