ADPW 2019: The growing importance of gut microbiota on digestive health

Gut microbiota in health and disease

The first symposium started with an insightful overview by Dr Holtmann from Australia. He emphasized that the large number of commensal bacteria normally residing in the human gut far exceeds the number of cells in the human body and drew attention to the key role microbes play in maintaining human health.

Gut microbes belong to three taxonomic classes: Bacteria, Archaea and Eukaryota; although most are difficult to cultivate, they perform the crucial functions of food digestion (especially fibre), production and absorption of vitamins, absorption of nutrients, protection of mucosa from pathogen colonization, regulation of the host immune system and intestinal peristalsis.

Dr Holtmann said that although stool microbiota collected from stools (luminal microbes) has until now been most researched, scientists are now recognizing the presence of a “mucosa-associated microbiote” that is more difficult to extract, characterize and culture, and yet seems to play a much stronger role in regulating our gut health and immune system.

There is growing evidence linking SIBO (small intestinal bacterial overgrowth) as well as dysbiosis associated with several diseases. Luminal antimicrobial therapy has been shown, for example, to improve liver functions in patients with chronic liver disease and primary sclerosing cholangitis, and the clinical response often noted in patients with irritable bowel syndrome (IBS)/disease (IBD).

He highlighted the strong links that have emerged between gut microbiota and a variety of gastro-intestinal (GI) and non- GI conditions, and showed growing evidence how interventions targeting gut microbiota could cure or control currently incurable diseases.

How to study the gut microbiota?

As the understanding of Gut microbiota is increasing, so are tools to study it. Dr Ayesha Shah from the University of Queensland discussed how traditional tools such as jejunal aspiration and breath tests are becoming outdated due to their bothersome methods or lack of specificity, and paving the way for newer culture-independent molecular methods such as bacterial density load (qPCR) and microbial community profiling using sequencing.

Prof. Peter Gibson from Melbourne while discussing the role of Gut microbiota modulation by way of treatment, spelt out what could be an ideal strategy. At the start one needs to define microbial or functional dysbiosis in the individual by analyzing the microbiota of the stool or biopsied mucosa or by functional assays of metabolites. This could help determine the desired change in Gut microbiota, such as altering the specific communities or the total abundance. Subsequently a method from the armantum catalogue could be employed to achieve the desired change, such as use of antibiotics, probiotics, diet or fecal microbiota transfer.

An example that he shared to drive home this approach included a method to increase diversity of gut bacteria by certain diets. Each food item, especially vegetables and fruits, seems to encourage growth of a select variety due to the type of prebiotics each contains; increasing the variety of vegetables and fruits in each meal could be a simple method of increasing diversity of flora in our guts.

Probiotics may help boost the relative abundance of specific bacteria for certain conditions. The ones that have been tested and proven to be of value include Bifidobacteria, Faecalobacterium prausnitzii, and certain species of Lactobacillus. On the other hand, antibiotics such as rifaximine can be used to reduce abundance of certain undesirable bacteria which breakdown sulphates or protein and be related to disease.

IBS, the commonest GI condition thought to be linked to food, and hence in turn, suspected to be contributed by the Gut microbiota, has been the subject of several RCTs using various probiotics such as different strains of Lactobacillus, Bifidobacteria, Saccharomyces and combination preparations. Despite the heterogeneity of the condition of IBS large and unlikeliness of large benefits, some probiotics have shown efficacy in RCTs: the front runner is a specific strain of Bifidobacterium infantis strain which fed for 4 to 8 weeks showed > 20% overall benefit in symptoms of pain, bloating and satisfaction of stool evacuation. Benefit was also noted with the use of a specific strain of B. animalis, and L. plantarum.

Antiobiotics and microbiota perturbation

The Biocodex Pharma symposium on “Antibiotics and microbiota perturbation” chaired by Dr Henry Cohen (Uruguay) and Dr Kentaro Sugano (Japan), was a well-attended and interesting session. Dr K.L. Goh (Malaysia) outlined the magnitude, diversity and role of Gut microbiota and highlighted two features by way of comparison: the microbial genome has around 3,300,000 genes compared with 22,000 genes of the human one, and the inter-individual difference was 80% in the former compared to 0.01% between human cells!

Disruption of this hugely biodiverse Gut microbiota by use of antibiotics has been shown to has been associated with several health issues. Apart from the commonly known consequence of encouraging and stimulating Clostridium difficile infection, it often leads to a state of dysbiosis, which in turn predisposes to developing a “leaky gut” and to immunoactivation.

Another major concern is acquisition/ transmission of antibiotic resistance by horizontal gene transfer. The perturbation of the innate gut flora and settlement of “abnormal” ones could predispose to a variety of disorders like obesity and diabetes as well.

Saccharomyces boulardii (Sb) has held sway as the prime remedy for treatment of AAD. Discovered in 1920 by the French microbiologist Henri Boulard, this species has continued to prove useful in protecting the gut from perturbations caused by antibiotic use, and restore the disturbed state to normalcy.