Gelesis Holdings, Inc. presented new preclinical data showing weight loss and additional metabolic benefits in mice receiving a microbiota transplant from another group of mice, treated with one of the company's proprietary hydrogels. These metabolic benefits occurred while both groups of mice, the donors of the microbiota transplant and the recipient mice, were on a high fat, high carbohydrate diet typically causing rapid weight gain, obesity, and diabetes. The findings were presented on June 4, 2022 at the American Diabetes Association's annual conference.
Gelesis' superabsorbent hydrogels are inspired by the composition (cellulose structures holding water) and mechanical properties (elasticity or firmness) of ingested raw vegetables. They are taken by capsules with water before a meal to create a much larger volume of small, non-aggregating hydrogel pieces that act locally in the digestive system without adding any additional calories. One of the hydrogels is commercially available as Plenity® to aid in weight management; others that utilize the same platform technology are in clinical and preclinical studies.

In April, Gelesis presented preclinical data at the World of Microbiome conference suggesting that adding superabsorbent hydrogel (Gel-B, an investigational candidate) to a high-fat “western-like” diet prevents unfavorable changes in the communities of gut bacteria associated with diet-induced weight gain. The study showed a striking effect on gut microbiota composition with enrichment of several key bacteria such as Akkermansia muciniphila, a bacterial species associated with gut health and weight loss. Importantly, an addible fiber (a modified cellulose), used as a positive control, did not support the growth of these species. This same type of modified cellulose is used to create Gelesis' proprietary hydrogels. The difference in bacterial growth between the linear fiber and the 3-dimensional hydrogel suggests that the effects of the hydrogel on the microbiota are mainly mechanical (i.e. elastic response or firmness). In previous studies, administration of one of these hydrogels, in addition to a high-fat diet, blunted weight gain, reversed gut atrophy, improved metabolic parameters, and restored gut barrier.

This new study aimed to investigate whether transferring the microbiota from Gel B-treated mice into the gut of mice fed a high fat, high carbohydrate, high cholesterol (HFHCC) diet for 10 weeks could alleviate the detrimental effects of their diet.
The study used intestinal microbiota transfer (IMT) to investigate the functional role of the gut microbiota to explain the metabolic effects associated with Gel-B treatment. Metabolic disease was induced in two cohorts of mice (“Donors” and “Recipients”) via consumption of a high fat, high cholesterol, high carbohydrate diet for 10 weeks. Donors either continued HFHCC or were treated with HFHCC plus Gel-B for 6 additional weeks. Fecal samples were processed from Donors every other day during weeks 2-6 of treatment. Recipients received either intestinal microbiota transfer from Gel-B-treated or untreated Donors. Recipients receiving IMT from untreated Donors continued to gain weight, while Recipients receiving IMT from Gel-B treated Donors lost weight, despite the continued consumption of HFHCC. Treating the recipients with intestinal microbiota of Gel B treated donors also resulted in improvement in glycemic control.