The intestinal microbiota: a one-of-a-kind therapeutic tool 

Published on October 9th, 2020, by Labtoo's team

The intestinal microbiota is composed of microorganisms (bacteria, fungus, virus, protists) whose role is more and more known and documented. Closely related to its host’s immune and digestive capacities, microbiota has been the subject of abundant research, particularly on inflammatory and autoimmune diseases.


Zoom on the intestinal microbiota in humans

Several microflorae exist in humans, depending on their location: intestinal, cutaneous, male genital, vaginal, etc. The intestinal microbiota is probably the most well-known one, but also the biggest of them all: from 1012 to 1014 microorganisms depending on the individuals, it weighs around two kilograms of commensals, mainly located on the luminal side of the digestive tract. It is extensively distributed between the small intestine and the colon, on the surface of the intestinal mucus. The progress made in high throughput sequencing has allowed to a better understanding of interactions between the intestinal microbiota and its host; it is now accurately described that the microbiota carries immune, digestive, metabolic and neurologic functions on the human body. A healthy person carries around 160 species of bacteria, and half of them are commonly found on other individuals. Most of these bacteria are anaerobic. Viruses and fungus composing the intestinal microbiota are not as diverse as bacteria, but the variety of the intestinal ecosystem depends on biological, cultural and socioeconomical factors (age, sex, lifestyle, hygiene, nutrition, …)


An individual’s microbiota is formed at birth on contact with the vaginal flora for a vaginal delivery, or on contact with the environmental microorganisms for those born by caesarian delivery. The bacterial colonization is progressive, in a specific order: the first intestinal bacteria which colonize a newborn are aerobic, like enterococcus and staphylococcus. By consuming the local oxygen, they foster anaerobic bacteria to develop, such as those from the bacteroides, clostridium and Bifidobacterium genera. Under the influence of dietary diversification, genetics, hygiene, received medical treatments and the person’s environment, the microbiota’s composition qualitatively and quantitatively evolves during the first years of life until it stabilizes. The fluctuation of sexual hormones levels can also have an impact on its composition. Taking specific medical treatments or modifying one’s health practices for a certain period of time may sustainably affect the intestinal microbiota. For example, an antibiotic treatment reduces the quality and quantity of the microbiota for a few days to several weeks. Most initial bacteria species can quickly recover, but some may not survive the treatment. Repeated and successive antibiotic therapies can therefore induce major and irremediable changes in the microbiota’s composition that might be detrimental for its host.


A pathogenic and therapeutic role at the same time

The intestinal microbiota plays a direct role in the digestive process: hydrolysis of non-digestible molecules (starch, vegetal polysaccharides), fermentation of non-digestible substrates, nutrients absorption by enzymatic reaction, metabolic regulation, etc. The microbiota also fosters bowel motility and the irrigation of intestinal epithelium; it also holds an important role in the immune system. Intestinal commensals fight against pathogenic agents and allow organs and immune elements to mature such as Peyer’s patches, lymphocytes, spleen and lymph nodes. These different functions of the microbiota allow him to exert a positive or negative influence on the organism, depending on its composition.

A disequilibrium between proinflammatory and anti-inflammatory bacterial species, as well as the predominance of certain bacteria genera (enterobacteria, fusobacteria) or a depletion in other species (Clostridia, Faecalibacterium), have been described in people with inflammatory bowel disease.

The intestinal microbiota is also involved in some metabolic diseases such as diabetes and obesity. Chronic inflammation, caused by Gram-negative bacteria constantly releasing LPS, fosters insulin resistance that might lead to diabetes and obesity. An increased permeability of the intestinal epithelium could also allow bacteria and their metabolites to go through the organism, thus creating inflammation spots throughout the body.

The intestinal microbiota possesses a major role in the gut-brain axis. It could be a potential risk factor or an improvement factor of psychiatric and neurodegenerative disorders, such as schizophrenia, autism, Alzheimer’s and Parkinson’s diseases, and anxiety disorders. New therapeutic perspectives involving the microbiota are coming to light (probiotics and antibiotics delivery for example), but many studies and trials have to be conducted in order to precisely determine the microbiota’s effects on these pathologies.

In oncology, the microbiota operates on two levels: at the carcinogenesis level itself, and on the efficacy of cancer drugs. Some tumors might be linked to the presence of specific microorganisms or of a dysbiosis in the intestines. Studies have also shown that frequent use of antibiotics on mice leads to an increase in the incidence and severity of mammal tumors. A synergistic action between cancer drugs and the intestinal microbiota could also exist; this could be particularly the case between cyclophosphamide and immunotherapies with the intestinal flora.


New therapeutic approaches

Diseases induced or maintained by a dysbiosis could be healed with six different therapeutic approaches:
  • A diet fostering the development of beneficial bacteria for the digestive system.
  • An antibiotic treatment targeting harmful microorganisms involved in the disease’s physiopathology. However, this option can not be considered as a chronic treatment due to a strong selection pressure.
  • The intake of probiotics, nonpathogenic and demonstrated to be beneficial for the intestinal flora.
  • The intake of probiotics, non-digestible feed components, useful for the growth or activity of specific bacterial populations.
  • The intake of symbiotics, combining both pre and probiotics.
  • Fecal transplantation, which consists in administering a bacterial suspension derived from a healthy person’s feces with a nasogastric tube or an enema. This option is already in use and efficient against severe intestinal infections caused by Clostridium difficile.

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