Cell Reports Medicine: Gelesis’ Oral Therapeutic Hydrogel Promotes Weight Loss & Metabolic Health by Targeting the Gut-Liver Axis

A new paper published today in Cell Reports Medicine suggests that weight loss resulting from Gelesis’ superabsorbent hydrogel treatment not only a result of its space-occupying properties; the mechanical composition and structure of the material may have notable benefits for gut and metabolic health.

OSH consistently resulted in weight loss, improved insulin sensitivity, and prevented the progression of NAFLD. Notably, the hydrogel induced endogenous GLP1 together with rapid, unique, and consistent changes in the gut microbiota composition, specifically fostering the growth of Akkermansia muciniphila, which is thought to be a promising new therapeutic for metabolic disorders. Here is a closer look.

Impact of the Western Diet

The continued rise in obesity and type 2 diabetes has led to the increasing prevalence of fatty liver disease worldwide and highlights the urgent need for therapies that can address the problem. Diets rich in fat, sugars, and ultra-processed foods are a contributor to rising obesity rates. These high fat/high carb diets have profound negative impacts on the host gut barrier function and microbial structure. This in turn has a detrimental effect and can lead to increased gut permeability and higher instances of metabolic disorders like obesity, diabetes, and fatty liver.

Reports have shown that the disruption of the intestinal barrier is a prerequisite for the onset of metabolic disorders. Indeed, the intestinal barrier is the first line of defence from external harmful molecules, where the mucus layer plays a frontline role in protecting the underling epithelial layer.

The Western Diet can thin-up the mucus, making the layers below more accessible to external harmful stimuli.

This in turn leads to a disruption of the epithelial barrier integrity, inducing a leakage in the tight junctions, which are responsible of the maintenance of the epithelium tightness and the regulation of nutrient fluxes and gut permeability.

Altered gut barrier permeability allows, in turn, for the translocation of bacteria and bacteria derived molecules into the host circulation, inducing a low-grade inflammation status, which is believed to signal and sustain the ?development of metabolic disorders.

Low grade inflammation, together with the lipid accumulation in the circulation and peripheral tissues, leads to the recruitment of the inflammatory cells and the progression of liver steatosis towards NAFLD/NASH.

The authors sought to evaluate the therapeutic potential and mechanism of action of a cellulose based oral super-absorbent hydrogel (OSH), engineered to provide a new non systemic approach for obesity

The authors demonstrated that OSH administration was able to modulate gut microbiota composition restoring Firmicutes/Bacteriodates ratio, reducing Actinobacteria and enriching Verrucomicrobia and restore intestinal mucus barrier. In particular, OSH was able to foster Akkermansia muciniphila expansion, a bacterium with a key role in metabolic diseases known for its positive impact on body weight loss and insulin sensitivity.

The hydrogels helped re-establish the mucus barrier further and maintained the integrity of the intestinal epithelial barrier, protecting tight junction firmness and restoring gut barrier permeability.

These OSH-induced changes result in the protection from inflammatory microbial molecules translocation to the host circulation and a reduction of peripheral lipid accumulation and inflammation. Finally, blocking the progression of NAFLD.

The authors conclude that OSH promotes gut microbiota changes, inducing the expansion of species beneficial for metabolic function. They also confirmed direct interplay between OSH and the gut by affecting both mucosal and epithelial barriers, counteracting low grade inflammation.

In summary, the work demonstrates the potential of oral superabsorbent hydrogels to be an effective and non-invasive therapeutic tool in the treatment of obesity and metabolic disorders. The work shows the potential of oral superabsorbent hydrogels to be an effective and non-invasive therapeutic tool in the long-term treatment of obesity and metabolic disorders.

You can read more in Cell Reports Medicine here .