Could the gut microbiome help manage diabetes?

June 10, 2019 | Disease

Melanie senior

Diabetes remains one of the most prevalent and costliest disorders, despite a wide palette of available treatments.

Leading diabetes players continue to churn out more convenient versions of their drugs, grappling for share in a highly competitive, price-pressured market.  Novo Nordisk recently invested in a short-cut route-to-market for its oral GLP-1 agonist, semaglutide, buying a priority review voucher from another company that may allow it to launch three months earlier.

GLP-1 agonists, like Novo’s own once-daily injectable, Victoza, have proven effective among many thousands of patients. They can help delay patients’ move onto insulin, and are much easier to use.

But the growth in diabetes prevalence means that new approaches are needed. Drugs are effective when they’re taken properly, but most often, they aren’t. Technology is helping – “intelligent” insulin pens, connected glucose monitors and apps to encourage healthy behavior and medication adherence are proliferating. The diabetes challenge has also drawn in behavioural psychologists and urban planners.

The gut microbiome may be the next frontier in battling diabetes. Research is uncovering a key role for the gut flora in many diseases, not just gastro-intestinal conditions but also cancers, auto-immune, endocrine and even central nervous system disorders. Gut bacteria are now understood to communicate with the brain and influence behavior – including, in some cases, by generating neurotransmitters like serotonin, gamma-aminobutyric acid (GABA) or dopamine.

An imbalance in the gut microbiome has already been associated with the development of insulin resistance in Type 2 (acquired) diabetes. Shifts in the gut microbiota can alter host metabolism – shifting it toward greater energy-harvesting and fat-deposition, for instance, or, potentially, driving appetite even when energy stores are replete.

The precise mechanisms and molecules involved, along with causal links, remain to be figured out. But it seems intuitive that gut health will impact diabetes, not least as this is a disease exacerbated by a high-fat diet. If, as is now believed, the gut influences behavior too, then a gut-microbiome-targeted approach could provide an effective solution for the many diabetics who cannot control their condition using existing therapies and tools.

Novo has been working since mid-2018 with Kallyope to uncover novel peptides to treat diabetes and obesity. New York City-based Kallyope is one of a handful of biotech companies seeking new therapeutic approaches through harnessing the “gut-brain axis” – the multiple two-way communication channels (neuronal, endocrine and humoral) between head and stomach.

The effort is still in discovery. But if drugs or nutritional supplements could be found that modulate both physiology (blood sugar regulation, energy homeostasis, insulin resistance) and psychology (appetite, willpower), this could prove a very useful addition to the diabetes toolbox.  

TargEDys in France already markets an appetite-regulating probiotic, ProbioSatys. Available over-the-counter, it allegedly promotes a feeling of fullness by providing a protein, ClpB, which mimics a satiety hormone called alpha-MSH. ClpB is produced naturally by certain types of gut bacteria. Its action is two-pronged – it enters the blood stream to act directly on the central nervous system, but also stimulates intestinal endocrine cells to produce more alpha-MSH. ProbioSatys is designed to enhance those natural regulatory pathways.

A trial is underway among 236 overweight people, to assess the supplement’s impact on weight, as well as its tolerability and safety, over a 12-week period versus placebo. The estimated completion date is August 2019, according to clinicaltrials.gov.