Finding. Cholera toxin, given alone, is a metabolic drug. Roginski, Mana, Florsheim and colleagues give mice one oral dose with no antigen and, within 24 hours, rewrite intestinal immunity, epithelium, microbes, liver, and whole-body energy use. Jejunal transcriptomes turn on inflammatory defense, glycolysis, autophagy, and lipid utilization, and they turn off proliferative and mitochondrial programs. The body goes hypometabolic even though hypothermia depends on strain. The liver conserves one mark across sexes and strains: Cyp7a1 goes down. Immune shifts include more epithelial group 3 innate lymphoid cells, fewer lamina-propria RORγt-positive regulatory T cells, and, in males of both strains, fewer epithelial ILC1/NK cells. Tuft cells (DCLK1) rise; MUC2 staining falls.
Why this paper matters
CTx is in every mucosal-adjuvant freezer. This preprint says the toxin is not a blank immune spark. It suppresses mitochondrial programs in the jejunum and quiets whole-body metabolism on the same day it moves tuft cells and ILCs. If you use CTx to adjuvant a vaccine and then measure host metabolism or intestinal mitochondria, you need this map.
What they actually measured
Integrated physiology, jejunal RNA-seq, imaging, immune profiling, hepatic genes, microbiome, two strains, both sexes. Mitochondria are a suppressed program, not a respirometry figure in the abstract.
How to read the score
Mid 70s. Real mitochondrial-program suppression plus systemic hypometabolism, transcriptional gut evidence. Confidence is medium for organelle function.
Caveats
No jejunal Seahorse. Adjuvant protocols vary. Sex and strain shape the immune half more than the Cyp7a1 half.
What to do with it
If you adjuvant with CTx, add a 24-hour metabolic cage and a jejunal mitochondrial gene-set check before you blame the antigen. Pull Cyp7a1 as a conserved hepatic marker. Do not call CTx a mitotoxin from this brief.