Lean microbiota: Gelesis research uncovers link between healthy gut microbiome and weight management

06 Jun 2022 --- Gelesis, maker of Plenity – an FDA-cleared weight management treatment – has presented new preclinical data evidencing its product’s efficacies. In particular, its research examines weight loss and additional metabolic benefits in mice receiving a microbiota transplant from another group of mice, treated with one of its proprietary hydrogels.

These metabolic benefits occurred while both groups of mice – the donors of the microbiota transplant and the mice receiving the microbiota transplant – were on a high fat, high carbohydrate diet typically causing rapid weight gain, obesity and diabetes, as a control measure.

“This study provides strong evidence that the modulation of the gut microbiome by Gelesis’ superabsorbent hydrogel [Gel-B, an investigational candidate] likely plays a mechanistic role in the weight loss and metabolic impact of this intervention,” says Dr. Maria Rescigno, PhD, group leader of the Mucosal Immunology and Microbiota Unit at Humanitas University (Milan, Italy) and one of the lead investigators on the study.

“We found that the microbiota from animals with obesity consuming a high-fat diet can be modified with Gel-B treatment to become a ‘lean microbiota.’ We then found that this Gel-B induced lean microbiota was transmissible, as it caused weight loss in mice with obesity that were not treated by Gel-B.”

The findings were presented at the American Diabetes Association’s annual conference.

Gelesis presented preclinical data suggesting that adding superabsorbent hydrogel to a high-fat diet prevents unfavorable changes in the communities of gut bacteria associated with diet-induced weight gain.Weight control functionalities of superabsorbent hydrogels
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 under the brand 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 suggesting that adding superabsorbent hydrogel to a high-fat “western-like” diet prevents unfavorable changes in the communities of gut bacteria associated with diet-induced weight gain. 

Alleviating detrimental diet effects
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 ten 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 ten weeks. 

Donors either continued HFHCC or were treated with HFHCC plus Gel-B for six additional weeks. Fecal samples were processed from Donors every other day during weeks two to six 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.

Research uncovers “striking effect” on gut
The study revealed 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 edible 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 three-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.

Exploring gut-metabolism synergies
The link between the human gut microbiome and metabolic function is increasingly coming to light with new clinical research shining light on related health outcomes.

Last month, Canada-based Lallemand Health Solutions’ patent-pending probiotic strain L. rhamnosus HA-114, was found to provide physical and mental health benefits for people in an overweight program. The ingredient is the “first of its kind” to help people in a weight management program restrain themselves from overeating.

Separate research has uncovered that Beneo’s Palatinose and chicory root fiber Orafti Synergy1 have a synergetic effect in impacting both blood glucose and the microbiota, contributing to overall metabolic health.

Edited by Benjamin Ferrer