Biomimetic superabsorbent hydrogel acts as a gut protective dynamic exoskeleton improving metabolic parameters and expanding A. muciniphila.

The rising prevalence of obesity and metabolic disorders worldwide highlights the urgent need to find new long-term and clinically meaningful weight-loss therapies. Here, we evaluate the therapeutic potential and the mechanism of action of a biomimetic cellulose-based oral superabsorbent hydrogel (OSH). Treatment with OSH exerts effects on intestinal tissue and gut microbiota composition, functioning like a protective dynamic exoskeleton. It protects from gut barrier permeability disruption and induces rapid and consistent changes in the gut microbiota composition, specifically fostering Akkermansia muciniphila expansion. The mechanobiological, physical, and chemical structures of the gel are required for A. muciniphila growth. OSH treatment induces weight loss and reduces fat accumulation, in both preventative and therapeutic settings. OSH usage also prevents liver steatosis, immune infiltration, and fibrosis, limiting the progression of non-alcoholic fatty liver disease. Our work shows the potential of using OSH as a non-systemic mechanobiological approach to treat metabolic syndrome and its comorbidities.
Competing Interests: Declaration of interests A. Silvestri, A.G.-G., M.V., D.B., P.B., I.S., G.F., J.M., S.C., M.L., M.R.-G., G.P., and M.R. declare that this work has been supported by funding provided by Gelesis S.r.l. B.J. is employed by Gelesis, Inc., and owns stock options. C.D., M.M., and A. Sannino are employed by Gelesis S.r.l.; C.D., A. Sannino, and M.R. own Gelesis, Inc., stock options. M.R., A. Silvestri, A. Sannino, and C.D. are inventors on patent US 10695363 “Compositions and methods for treating or preventing gut permeability-related disorders” (applicant: GELESIS LLC, Boston MA, USA).
(Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)