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Guest commentary: New facts about the gut microbiome that may be surprising
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In this guest commentary, Samantha Nazareth, MD, FACG, a gastroenterologist in private practice, offers several take-home messages from the Gut Microbiota for Health World Summit 2019, organized by the American Gastroenterological Association (AGA) and the European Society of Neurogastroenterology and Motility (ESNM). As Nazareth noted, some of the takeaways may be surprising.
The microbiome sleeps, too
We know that central circadian rhythms have an immense effect on metabolism by influencing both insulin sensitivity and fat storage. Beyond our central circadian rhythm, the gut microbiota also has an endogenous circadian rhythm. “The host is periodically exposed to different bacterial numbers, species, functions and products at different times of the day” and these oscillations of microbiota metabolome seem to be triggered by feeding times and food composition.
Traveling metabolites
Metabolites from the gut microbes act as signals not just locally, but also distally in the liver. These gut microbes’ metabolites can synchronize or de-synchronize liver gene transcription and in turn affect the liver’s metabolism of drugs, dietary components and xenobiotics. Antibiotics disrupt these native metabolite rhythms — uncoupling gut microbiome rhythm from the liver’s circadian rhythms.
Beyond conventional microbiome testing
Using stool is the most accessible sample for microbiome testing, but it may or may not be the most relevant microbiome to study. Beyond luminal microbiome (which a stool sample provides), there are different microbiomes in the mucosal layer (in biofilm), more invasive at the mucosa, and in the small intestine. Some considerations — how do we consistently measure a microbiome in the location of interest, or do we continue to infer based on luminal microbiome sampling from the rectum?
What the heck is dysbiosis?
As Jack Gilbert, PhD, pointed out in his keynote speech, “it is a definable state with mechanistic implications, not just a change in microbial diversity.” There is an underlying defect that impairs the host’s ability to control the native microbiome. This defect, in turn, changes metabolites, which can contribute to symptoms and disease.
Darwinian microbes
Besides producing beneficial metabolites, a balanced microbiome actively engages and competes with pathogenic species. The microbes interact with the host through receptors on the intestinal epithelial lining, which communicate via dendritic cells that govern the systemic immune system and “provide health-promoting influences on overall host health maintenance.”
The Wild Wild West
Fecal microbiota transplantation (FMT) is an investigational therapy that can be used by physicians to treat recurrent Clostridioides difficile without an investigational new drug (IND) permit. Beyond this indication, there are no other FDA regulated interventions to manipulate the microbiome (probiotics are currently only available as dietary supplements, which means they are not required to undergo rigorous clinical testing like drugs and biologics). There are currently no normal ranges for any individual microbial taxa. And, the notion of good vs. bad bugs needs to be refuted.
Fiber matters
Fiber-deprived diets lead to increased microbes that breakdown mucin. Mucin protects the gut from pathogenic load during infection and thus, lack of fiber increases pathogen susceptibility.
Gut microbes to treat cardiometabolic diseases
Gut microbes are involved in the metabolism forming trimethylamine N-oxide (TMAO), which has been linked to increased risk for cardiovascular events. A novel intervention would be to target the composition of the microbiome or their biochemical pathways with either a probiotic or other treatment to interfere with metabolic pathways and effectively change the level of risk for cardiometabolic diseases for the host.
Microbiome testing for NASH
Microbiome testing may be another screening method for NAFLD vs. NASH in the next 5 to 10 years. There are clear differences in the gut microbiome in those with NAFLD vs. NASH vs. advanced fibrosis of NASH – there’s a decrease in microbial diversity, higher Enterobacteriaceae and Streptococcus, and shift toward more gram-negative microbes as it progresses toward advanced fibrosis.
I suspect that next year we will be discussing postbiotics or psychobiotics.
Check out #GMFH2019 to see what else you missed out. You can review additional takeaways from the meeting and watch session recordings on AGA’s website.