D-Mannose treats obesity by increasing adipose Treg cells and suppressing gut Firmicutes

Zanvit, P.; Xu, J.; Guo, N.; Zhang, D.; Prochazkova, M.; Gauthier, T.; Patel, D. P.; Cain, A.; Jin, W.; Bynum, A.; Gonzalez, F. J.; Belkaid, Y.; Chen, W.

doi:10.64898/2026.08.10.743951

bioRxiv · 10.64898/2026.08.10.743951

D-Mannose treats obesity by increasing adipose Treg cells and suppressing gut Firmicutes

Zanvit, P.·Xu, J.·Guo, N.·Zhang, D.·Prochazkova, M.·Gauthier, T.·Patel, D. P.·Cain, A.·Jin, W.·Bynum, A.·Gonzalez, F. J.·Belkaid, Y.·Chen, W.

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Abstract

Early-life microbiota represent an indispensable factor for the proper development and function of host metabolism and the immune system. We have demonstrated that neonatal exposure to antibiotics for the first 3 weeks (NeoATB) leads to obesity in adulthood, characterized by gut microbiota dysbiosis and dysregulated immune responses. Here, we demonstrate that feeding D-mannose suppresses NeoATB-induced obesity, accompanied by improved glucose tolerance and decreased insulin resistance. Mechanistically, D-mannose feeding decreased hypoxia and increased oxygenation and recovery of metabolic activity of adipocytes. D-mannose restored CD4+Foxp3+ST2+ Tregs, leading to a reduction of Th1 pro-inflammatory cells in the adipose tissue of NeoATB mice. Significantly, we revealed that D-mannose treatment reversed the dysregulated ratios of phylum Firmicutes to phylum Bacteroidetes in obese NeoATB mice, which was surprisingly attributed to D-mannose-mediated suppression of the growth of Firmicutes rather than an increase in the growth of Bacteroidetes. These findings should have therapeutic implications for the treatment of obesity in human patients.

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Zanvit, P., Xu, J., Guo, N., Zhang, D., Prochazkova, M., Gauthier, T., Patel, D. P., Cain, A., Jin, W., Bynum, A., Gonzalez, F. J., Belkaid, Y., Chen, W.. 2026-08-18. D-Mannose treats obesity by increasing adipose Treg cells and suppressing gut Firmicutes. https://doi.org/10.64898/2026.08.10.743951

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