Tuesday, October 4, 2022


Biotechnology News Magazine

Microbiota Transplantation Demonstrates How Gut Bacteria Contributes to Weight Loss and Beneficial Metabolic Effects with Gelesis’ Proprietary Hydrogel

New preclinical data presented today at the American Diabetes Association’s annual conference suggests that the company’s superabsorbent hydrogel causes changes to the microbiota leading to weight loss and improvements in glucose tolerance and insulin sensitivity

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Gelesis (NYSE: GLS), the maker of Plenity for weight management, 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 today 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.

“This study provides strong evidence that the modulation of the gut microbiome by Gelesis’ superabsorbent hydrogel likely plays a mechanistic role in the weight loss and metabolic impact of this intervention,” said Maria Rescigno, PhD, Group Leader of the Mucosal Immunology and Microbiota Unit at Humanitas University in Milan, 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 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.

An interview with study author Dr. Rescigno is available at https://youtu.be/AsmUo7lnQbs.

About Gelesis

Gelesis Holdings Inc. (NYSE: GLS) (“Gelesis”) is a consumer-centered biotherapeutics company and the maker of Plenity®, which is inspired by nature and FDA cleared to aid in weight management. Our first-of-their-kind non-systemic superabsorbent hydrogels are made entirely from naturally derived building blocks. They are inspired by the composition and mechanical properties of raw vegetables, taken by capsule, and act locally in the digestive system, so people feel satisfied with smaller portions. Our portfolio includes Plenity® and potential therapies in development for patients with Type 2 Diabetes, Non-alcoholic Fatty Liver Disease (NAFLD)/Non-alcoholic Steatohepatitis (NASH), and Functional Constipation. For more information, visit gelesis.com, or connect with us on Twitter @GelesisInc.

Plenity® is indicated to aid weight management in adults with excess weight or obesity, a Body Mass Index (BMI) of 25–40 kg/m², when used in conjunction with diet and exercise.

Important Safety Information about Plenity

  • Patients who are pregnant or are allergic to cellulose, citric acid, sodium stearyl fumarate, gelatin, or titanium dioxide should not take Plenity.
  • To avoid impact on the absorption of medications:
    • For all medications that should be taken with food, take them after starting a meal.
    • For all medications that should be taken without food (on an empty stomach), continue taking on an empty stomach or as recommended by your physician.
  • The overall incidence of side effects with Plenity was no different than placebo. The most common side effects were diarrhea, distended abdomen, infrequent bowel movements, and flatulence.
  • Contact a doctor right away if problems occur. If you have a severe allergic reaction, severe stomach pain, or severe diarrhea, stop using Plenity until you can speak to your doctor.


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