Interplay Between the Gut Microbiome and Typhoid Fever: Insights from Endemic Countries and a Controlled Human Infection Model

Typhoid fever is a systemic infection caused by Salmonella enterica serovar Typhi (S. Typhi) bacteria invading through the gut lumen. Transmission occurs through ingestion of contaminated food and water, particularly in settings with poor water, sanitation and hygiene infrastructure, resulting in over 10 million illnesses annually. It is well established that vaccines and natural infections can stimulate protective immunity against S. Typhi. As the pathogen invades through the gastrointestinal tract, it is plausible that the gut microbiome may also influence the outcome of S. Typhi exposure. There is some evidence that bacteria producing short-chain fatty acids (SCFAs) may create an environment unfavourable to invasive Salmonella, but data from humans is very limited.