Cholera toxin remodels intestinal immunity and suppresses systemic metabolism
- 1Arizona State University, School of Life Sciences
Abstract
Cholera toxin (CTx) is a potent enterotoxin and widely used mucosal adjuvant, yet the acute host response to CTx itself, in the absence of a co-administered antigen, remains vague. In this study, we integrated physiological and metabolic phenotyping with intestinal transcriptomics, epithelial imaging, immune profiling, hepatic gene-expression analysis, and paired microbiome profiling to characterize the response to a single oral CTx exposure in mice. Within 24 h, CTx remodeled immune-cell composition in both epithelial and lamina propria compartments, with responses shaped by sex and genetic background. Recurrent changes included increased epithelial group 3 innate lymphoid cells, reduced lamina propria ROR{gamma}t+ regulatory T cells, and decreased epithelial ILC1/NK cells in males of both strains. CTx also increased villus DCLK1+ tuft cells and reduced MUC2 immunoreactivity. Jejunal transcriptomics revealed induction of inflammatory defense, glycolytic, autophagy, and lipid-utilization programs together with suppression of proliferative and mitochondrial programs, consistent with coordinated stress adaptation. These local changes were accompanied by rapid restructuring of the fecal microbial community and by systemic hypometabolism, despite markedly different hypothermic responses across strains. CTx also elicited a selective hepatic stress and metabolic program, including conserved suppression of Cyp7a1 across sexes and strains. Together, these findings show that CTx alone rapidly reorganizes the intestinal immune, epithelial, metabolic, and microbial environment while suppressing whole-body metabolism. This work provides an integrated framework for understanding the acute host response to CTx and for interpreting its widespread use as a mucosal adjuvant.
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BibTeX
@misc{roginski2026cholera,
title = {{Cholera toxin remodels intestinal immunity and suppresses systemic metabolism}},
author = {A. C. Roginski and M. Godazgar and C. L. Salgado and G. Lahiri and C. Woodrow and T. Hartley McDermott and B. G. Costa Lima and G. P. Rodriguez-Castano and L. Voth-Gaeddert and H. Borges da Silva and M. O. Dietrich and M. D. Mana and E. B. Florsheim},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.29.755509},
url = {https://www.biorxiv.org/content/10.64898/2026.09.29.755509v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Cholera toxin remodels intestinal immunity and suppresses systemic metabolism
AU - A. C. Roginski
AU - M. Godazgar
AU - C. L. Salgado
AU - G. Lahiri
AU - C. Woodrow
AU - T. Hartley McDermott
AU - B. G. Costa Lima
AU - G. P. Rodriguez-Castano
AU - L. Voth-Gaeddert
AU - H. Borges da Silva
AU - M. O. Dietrich
AU - M. D. Mana
AU - E. B. Florsheim
PY - 2026
DA - 2026/09/29
PB - bioRxiv
DO - 10.64898/2026.09.29.755509
UR - https://www.biorxiv.org/content/10.64898/2026.09.29.755509v1
AB - Cholera toxin (CTx) is a potent enterotoxin and widely used mucosal adjuvant, yet the acute host response to CTx itself, in the absence of a co-administered antigen, remains vague. In this study, we integrated physiological and metabolic phenotyping with intestinal transcriptomics, epithelial imaging, immune profiling, hepatic gene-expression analysis, and paired microbiome profiling to characterize the response to a single oral CTx exposure in mice. Within 24 h, CTx remodeled immune-cell composition in both epithelial and lamina propria compartments, with responses shaped by sex and genetic background. Recurrent changes included increased epithelial group 3 innate lymphoid cells, reduced lamina propria ROR{gamma}t+ regulatory T cells, and decreased epithelial ILC1/NK cells in males of both strains. CTx also increased villus DCLK1+ tuft cells and reduced MUC2 immunoreactivity. Jejunal transcriptomics revealed induction of inflammatory defense, glycolytic, autophagy, and lipid-utilization programs together with suppression of proliferative and mitochondrial programs, consistent with coordinated stress adaptation. These local changes were accompanied by rapid restructuring of the fecal microbial community and by systemic hypometabolism, despite markedly different hypothermic responses across strains. CTx also elicited a selective hepatic stress and metabolic program, including conserved suppression of Cyp7a1 across sexes and strains. Together, these findings show that CTx alone rapidly reorganizes the intestinal immune, epithelial, metabolic, and microbial environment while suppressing whole-body metabolism. This work provides an integrated framework for understanding the acute host response to CTx and for interpreting its widespread use as a mucosal adjuvant.
ER -