Mon 29 Jun 2020
Good diagnostic tests to accurately assess the gut microbiome remain elusive
The gut microbiome continues to be a hot topic and many research studies are being published each month. Probiotic sales are booming in pharmacies and health shops. However, in the midst of all this enthusiasm a recent review of all the evidence for the benefit of probiotics for a range of gastrointestinal conditions has poured some cold water on the subject.
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The study was carried out by the American Gastroenterological Association Institute. The editorial in the journal Gastroenterology in which the study was published states; “over the last 25 years increased understanding of mucosal immunology and epithelial biology has opened new avenues of research into the presumed benefits of the main bacterial genera used in probiotics (e.g., Lactobacillus sp, Bifidobacterium sp, Streptococcus sp.). In model systems, probiotics have been shown to modulate the immune system, provide resistance to invasion by pathogens, improve intestinal barrier function, lower the pH of the gut, and modulate intestinal motility and pain perception. Yet, despite a number of animal studies showing how probiotic bacteria can alleviate diseases ranging from autism to osteoporosis, translation of these findings into human clinical trials that has efficacy has been slow to emerge. The most likely reasons for lack of progress include scant high quality human clinical trials, scientific misconceptions, and absence of appropriate regulation of probiotics.”
Only two findings could be made with any confidence; “First, the Institute found moderate evidence that probiotics do not reduce the duration or severity of diarrhea in children with acute infectious gastroenteritis. It is ironic that diarrhea in children was one of the original indications for potential therapy using probiotics over 100 years ago. However, only a minority of the studies tested strains of Bifidobacteria suggested by Tissier. In contrast, there was moderate to high level of evidence that probiotics containing different strains of Lactobacillus and Bifidobacterium genera were beneficial in preventing necrotizing enterocolitis (NEC), the most frequent and devastating gastrointestinal disease in preterm, low birthweight newborns and mitigating its complications.”
These findings are disappointing but reflect the complexity of the topic. Most gut microbiome tests identify species of bacteria present. However, it has become clear that the strain of any particular species that is present is important. For example, there are strains of the species E. coli that appear top be commensal and perhaps beneficial in the microbiome but there are also strains of E. coli that are very pathogenic and can cause severe disease.
It has also become apparent that there is enormous diversity in the microbiome between individuals in the same community. The bacteria in probiotic preparations are almost always species that are not adapted to living in the intestinal tract and studies have shown that they often do not survive and colonize the gut. Probiotic preparations are often prescribed to people after a course of antibiotics as it seems reasonable that they might help restore normality to the gut microbiome. One study showed that in some people the use of probiotics actually delayed the return of the normal gut microbiome.
The editorial concludes with a question and a suggested answer; “How can we move forward to better provide all of the various stakeholders with products that are properly vetted to have a bona fide impact on human health and disease? With next-generation sequencing technologies, germ-free animal platforms, novel genetic tools and methods for assaying the functions of communities of microbes, we now have the appropriate technology to provide a scientific basis for probiotic selection. These next-generation probiotics will need to be tested for safety and efficacy in well-designed and properly powered clinical trials.”
We may have to wait for a few more years before we can be confident that we have good diagnostic tests to accurately assess the gut microbiome and the complex interactions between species in the microbial community. It may take years before we have good data showing that particular therapeutic manipulations of the microbiome actually benefit the recipients.