Tobacco smoking disrupts bile acid and tryptophan metabolism in multiple sclerosis
Farren BS Briggs, Jevin Litwiler, Federico Montini, Mahboubeh Fereidan Esfahani, Jessica Sagen, Jacob L McCauley, Flavia Nelson, Simon Gregory, Roberta Brambilla, Erika S Trapl, Jessica N Cooke Bailey, Luke A Schwerdtfeger, Laura Cox, Howard Weiner, W Oliver TobinBackground:
Smokers with multiple sclerosis (MS) experience worse disease, yet underlying mechanisms remain unknown. Smoking disrupts bile acid and tryptophan metabolism in non-MS populations; both pathways involve host–microbiome co-metabolism and have been linked to MS.
Objective:
Determine whether smoking perturbs these metabolic pathways in MS and whether such alterations statistically mediate smoking’s effect on MS severity.
Methods:
We analyzed serum bile acid, tryptophan, and tobacco-related metabolites across four independent MS cohorts (
Results:
Current smokers and nicotine-exposed MS subjects had reductions in bile acids and tryptophan metabolites, notably indolepropionate, a neuroprotective, anti-inflammatory gut–microbial metabolite. Lower indolepropionate statistically mediated ~20% of smoking’s adverse effect on MS severity. Metagenomic analyses identified potential smoking-enriched MS-linked taxa, and that indolepropionate broadly co-occurs with microbial networks (e.g.
Conclusion:
Tobacco exposure disrupts host–microbiome tryptophan and bile acid metabolism in persons with multiple sclerosis, with indolepropionate depletion partially mediating disease severity, highlighting a potential mechanistic pathway warranting further investigation in MS smokers.