Interplay between the gut microbiome and typhoid fever: insights from endemic countries and a controlled human infection model
Abstract Background Typhoid fever is a systemic infection caused by Salmonella enterica serovar Typhi (S. Typhi) invasion from the gut lumen. Transmission between people occurs through ingestion of contaminated food and water, particularly in settings with poor water and sanitation infrastructure, r...
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2025-07-01
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| Series: | Microbiome |
| Online Access: | https://doi.org/10.1186/s40168-025-02125-7 |
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| author | Philip M. Ashton Leonardos Mageiros James E. Meiring Angeziwa Chunga-Chirambo Farhana Khanam Sabina Dongol Happy Banda Abhilasha Karkey Lorena Preciado-Llanes Helena Thomaides-Brears Malick Gibani Nazmul Hasan Rajib Nazia Rahman Prasanta Kumar Biswas Md Amirul Islam Bhuiyan Sally Kay Kate Auger Olivier Seret Nicholas R. Thomson Andrew J. Pollard Stephen Baker Buddha Basnyat John D. Clemens Christiane Dolecek Sarah J. Dunstan Gordon Dougan Robert S. Heyderman Virginia E. Pitzer Firdausi Qadri Melita A. Gordon Kathryn E. Holt Thomas C. Darton STRATAA Study Group |
| author_facet | Philip M. Ashton Leonardos Mageiros James E. Meiring Angeziwa Chunga-Chirambo Farhana Khanam Sabina Dongol Happy Banda Abhilasha Karkey Lorena Preciado-Llanes Helena Thomaides-Brears Malick Gibani Nazmul Hasan Rajib Nazia Rahman Prasanta Kumar Biswas Md Amirul Islam Bhuiyan Sally Kay Kate Auger Olivier Seret Nicholas R. Thomson Andrew J. Pollard Stephen Baker Buddha Basnyat John D. Clemens Christiane Dolecek Sarah J. Dunstan Gordon Dougan Robert S. Heyderman Virginia E. Pitzer Firdausi Qadri Melita A. Gordon Kathryn E. Holt Thomas C. Darton STRATAA Study Group |
| author_sort | Philip M. Ashton |
| collection | DOAJ |
| description | Abstract Background Typhoid fever is a systemic infection caused by Salmonella enterica serovar Typhi (S. Typhi) invasion from the gut lumen. Transmission between people occurs through ingestion of contaminated food and water, particularly in settings with poor water and sanitation infrastructure, resulting in over 10 million illnesses annually. As the pathogen invades via the gastrointestinal tract, it is plausible that the gut microbiome may 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 limited. Methods To investigate the association between the gut microbiome and typhoid fever, we analysed samples collected from three all-age cohorts enrolled in a prospective surveillance study conducted across three settings where typhoid fever is endemic (Dhaka, Bangladesh; Blantyre, Malawi; and Kathmandu, Nepal). Cohorts consisted of acute typhoid fever patients (n = 92), asymptomatic household contacts of typhoid fever patients (representing individuals who were likely exposed to S. Typhi but did not develop the disease, n = 97) and asymptomatic serosurvey participants with high Vi antibody titres (representing individuals who were exposed to S. Typhi and may be carriers, n = 69). The stool microbiomes of each cohort were characterised using shotgun metagenomics, and bacterial diversity, composition and function were compared. Results We identified 4 bacterial species that were significantly lower in abundance in typhoid fever patients compared with household contacts (i.e. probably exposed), in two of the three participant populations (Bangladesh and Malawi). These bacteria may represent taxa that provide protection against the development of clinical infection upon exposure to S. Typhi and include the inflammation-associated species Prevotella copri clade A and Haemophilus parainfluenzae. Our functional analysis identified 28 specific metabolic gene clusters (MGCs) negatively associated with typhoid fever in Bangladesh and Malawi, including seven MGCs involved in SCFA metabolism. The putative protection provided by microbiome SCFA metabolism was supported by data from a controlled human infection model conducted in a UK population, in which participants who did not develop typhoid fever following ingestion of S. Typhi had a higher abundance of a putative SCFA-metabolising MGC (q-value = 0.22). Conclusions This study identified the same protective associations between taxonomic and functional microbiota characteristics and non-susceptibility to typhoid fever across multiple human populations. Future research should explore the potential functional role of SCFAs and inflammation-associated bacteria in resistance to S. Typhi and other enteric infections. Video Abstract |
| format | Article |
| id | doaj-art-63cbbf32c28f4374bafe7cb1b43d74f4 |
| institution | Kabale University |
| issn | 2049-2618 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Microbiome |
| spelling | doaj-art-63cbbf32c28f4374bafe7cb1b43d74f42025-08-20T03:46:15ZengBMCMicrobiome2049-26182025-07-0113111610.1186/s40168-025-02125-7Interplay between the gut microbiome and typhoid fever: insights from endemic countries and a controlled human infection modelPhilip M. Ashton0Leonardos Mageiros1James E. Meiring2Angeziwa Chunga-Chirambo3Farhana Khanam4Sabina Dongol5Happy Banda6Abhilasha Karkey7Lorena Preciado-Llanes8Helena Thomaides-Brears9Malick Gibani10Nazmul Hasan Rajib11Nazia Rahman12Prasanta Kumar Biswas13Md Amirul Islam Bhuiyan14Sally Kay15Kate Auger16Olivier Seret17Nicholas R. Thomson18Andrew J. Pollard19Stephen Baker20Buddha Basnyat21John D. Clemens22Christiane Dolecek23Sarah J. Dunstan24Gordon Dougan25Robert S. Heyderman26Virginia E. Pitzer27Firdausi Qadri28Melita A. Gordon29Kathryn E. Holt30Thomas C. Darton31STRATAA Study Group32Malawi-Liverpool-Wellcome ProgrammeDepartment of Infectious Diseases, School of Translational Medicine, Monash UniversityMalawi-Liverpool-Wellcome ProgrammeMalawi-Liverpool-Wellcome ProgrammeInternational Centre for Diarrhoeal Diseases ResearchOxford University Clinical Research Unit, Patan Academy of Health SciencesMalawi-Liverpool-Wellcome ProgrammeOxford University Clinical Research Unit, Patan Academy of Health SciencesOxford Vaccine Group, Department of Paediatrics, University of OxfordOxford Vaccine Group, Department of Paediatrics, University of OxfordOxford Vaccine Group, Department of Paediatrics, University of OxfordInternational Centre for Diarrhoeal Diseases ResearchInternational Centre for Diarrhoeal Diseases ResearchInternational Centre for Diarrhoeal Diseases ResearchInternational Centre for Diarrhoeal Diseases ResearchWellcome Sanger InstituteWellcome Sanger InstituteWellcome Sanger InstituteWellcome Sanger InstituteOxford Vaccine Group, Department of Paediatrics, University of OxfordDepartment of Medicine, University of CambridgeOxford University Clinical Research Unit, Patan Academy of Health SciencesInternational Centre for Diarrhoeal Diseases ResearchNuffield Department of Medicine, Centre for Tropical Medicine and Global Health, University of OxfordDepartment of Infectious Diseases, The University of Melbourne at The Peter Doherty Institute for Infection and ImmunityDepartment of Medicine, University of CambridgeResearch Department of Infection, Division of Infection and Immunity, University College LondonDepartment of Epidemiology of Microbial Diseases, Yale School of Public Health, Yale UniversityInternational Centre for Diarrhoeal Diseases ResearchMalawi-Liverpool-Wellcome ProgrammeDepartment of Infectious Diseases, School of Translational Medicine, Monash UniversityClinical Infection Research Group, Division of Clinical Medicine, School of Medicine & Population Health, and The Florey Institute for Infection, University of SheffieldStrategic Typhoid Alliance Across Asia and Africa ConsortiumAbstract Background Typhoid fever is a systemic infection caused by Salmonella enterica serovar Typhi (S. Typhi) invasion from the gut lumen. Transmission between people occurs through ingestion of contaminated food and water, particularly in settings with poor water and sanitation infrastructure, resulting in over 10 million illnesses annually. As the pathogen invades via the gastrointestinal tract, it is plausible that the gut microbiome may 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 limited. Methods To investigate the association between the gut microbiome and typhoid fever, we analysed samples collected from three all-age cohorts enrolled in a prospective surveillance study conducted across three settings where typhoid fever is endemic (Dhaka, Bangladesh; Blantyre, Malawi; and Kathmandu, Nepal). Cohorts consisted of acute typhoid fever patients (n = 92), asymptomatic household contacts of typhoid fever patients (representing individuals who were likely exposed to S. Typhi but did not develop the disease, n = 97) and asymptomatic serosurvey participants with high Vi antibody titres (representing individuals who were exposed to S. Typhi and may be carriers, n = 69). The stool microbiomes of each cohort were characterised using shotgun metagenomics, and bacterial diversity, composition and function were compared. Results We identified 4 bacterial species that were significantly lower in abundance in typhoid fever patients compared with household contacts (i.e. probably exposed), in two of the three participant populations (Bangladesh and Malawi). These bacteria may represent taxa that provide protection against the development of clinical infection upon exposure to S. Typhi and include the inflammation-associated species Prevotella copri clade A and Haemophilus parainfluenzae. Our functional analysis identified 28 specific metabolic gene clusters (MGCs) negatively associated with typhoid fever in Bangladesh and Malawi, including seven MGCs involved in SCFA metabolism. The putative protection provided by microbiome SCFA metabolism was supported by data from a controlled human infection model conducted in a UK population, in which participants who did not develop typhoid fever following ingestion of S. Typhi had a higher abundance of a putative SCFA-metabolising MGC (q-value = 0.22). Conclusions This study identified the same protective associations between taxonomic and functional microbiota characteristics and non-susceptibility to typhoid fever across multiple human populations. Future research should explore the potential functional role of SCFAs and inflammation-associated bacteria in resistance to S. Typhi and other enteric infections. Video Abstracthttps://doi.org/10.1186/s40168-025-02125-7 |
| spellingShingle | Philip M. Ashton Leonardos Mageiros James E. Meiring Angeziwa Chunga-Chirambo Farhana Khanam Sabina Dongol Happy Banda Abhilasha Karkey Lorena Preciado-Llanes Helena Thomaides-Brears Malick Gibani Nazmul Hasan Rajib Nazia Rahman Prasanta Kumar Biswas Md Amirul Islam Bhuiyan Sally Kay Kate Auger Olivier Seret Nicholas R. Thomson Andrew J. Pollard Stephen Baker Buddha Basnyat John D. Clemens Christiane Dolecek Sarah J. Dunstan Gordon Dougan Robert S. Heyderman Virginia E. Pitzer Firdausi Qadri Melita A. Gordon Kathryn E. Holt Thomas C. Darton STRATAA Study Group Interplay between the gut microbiome and typhoid fever: insights from endemic countries and a controlled human infection model Microbiome |
| title | Interplay between the gut microbiome and typhoid fever: insights from endemic countries and a controlled human infection model |
| title_full | Interplay between the gut microbiome and typhoid fever: insights from endemic countries and a controlled human infection model |
| title_fullStr | Interplay between the gut microbiome and typhoid fever: insights from endemic countries and a controlled human infection model |
| title_full_unstemmed | Interplay between the gut microbiome and typhoid fever: insights from endemic countries and a controlled human infection model |
| title_short | Interplay between the gut microbiome and typhoid fever: insights from endemic countries and a controlled human infection model |
| title_sort | interplay between the gut microbiome and typhoid fever insights from endemic countries and a controlled human infection model |
| url | https://doi.org/10.1186/s40168-025-02125-7 |
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