Depletion of key gut bacteria predicts disrupted bile acid metabolism in inflammatory bowel disease
ABSTRACT The gut microbiome plays a key role in bile acid (BA) metabolism, where a diversity of metabolic products contribute to human health and disease. In particular, Inflammatory Bowel Disease (IBD) is characterized by a low concentration of secondary bile acids (SBAs), whose transformation from...
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| Language: | English |
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American Society for Microbiology
2025-02-01
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| Series: | Microbiology Spectrum |
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| Online Access: | https://journals.asm.org/doi/10.1128/spectrum.01999-24 |
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| author | Daniel Peterson Christopher Weidenmaier Sonia Timberlake Rotem Gura Sadovsky |
| author_facet | Daniel Peterson Christopher Weidenmaier Sonia Timberlake Rotem Gura Sadovsky |
| author_sort | Daniel Peterson |
| collection | DOAJ |
| description | ABSTRACT The gut microbiome plays a key role in bile acid (BA) metabolism, where a diversity of metabolic products contribute to human health and disease. In particular, Inflammatory Bowel Disease (IBD) is characterized by a low concentration of secondary bile acids (SBAs), whose transformation from primary bile acids (PBAs) is an essential function performed solely by gut bacteria. BA-transformation activity mediated by the bile acid inducible (bai) operon has been functionally characterized in the genus Clostridium, and homologous bai gene sequences have been found in metagenome-assembled genomes (MAGs) belonging to other taxa in the human gut, but it is unclear which species of bai-carrying bacteria perform physiologically significant amounts of bile acid transformation in healthy and sick individuals. Here, we analyzed hundreds of stool samples with paired metagenomic and metabolomic data from IBD patients and controls and found that the abundance of the bai operon in metagenomic samples was highly predictive of that sample’s high- or low-SBA metabolic state. We further found that bai genes from the Clostridium species best characterized as BA transformers were more prevalent in IBD patients than in non-IBD controls, while bai genes from uncharacterized taxa known only from MAGs were much more physiologically relevant in non-IBD samples. These un-isolated clades of BA-transforming bacteria merit further research; as beyond their prevalence in the human population, we found some cases in which they engrafted in IBD patients who had undergone fecal microbiota transplantation and experienced a clinical response.IMPORTANCEIn this paper, we identify specific bacteria that perform an important metabolic function in the human gut and demonstrate that in the guts of a large subset of patients with IBD, these bacteria are missing and the function is defective. This is a rare example where the correlation between the absence of specific bacteria and the dysfunction of metabolism is directly observed, not in mice nor in the lab, but in physiologic microbial communities in the human gut. Our results point to a path for studying how a small but important set of bacteria is affected by conditions in the IBD gut and perhaps to the development of interventions to mitigate the loss of these bacteria in IBD. |
| format | Article |
| id | doaj-art-8c2f4df2137c482ca930d1a56f66429e |
| institution | Kabale University |
| issn | 2165-0497 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | Microbiology Spectrum |
| spelling | doaj-art-8c2f4df2137c482ca930d1a56f66429e2025-02-04T14:03:40ZengAmerican Society for MicrobiologyMicrobiology Spectrum2165-04972025-02-0113210.1128/spectrum.01999-24Depletion of key gut bacteria predicts disrupted bile acid metabolism in inflammatory bowel diseaseDaniel Peterson0Christopher Weidenmaier1Sonia Timberlake2Rotem Gura Sadovsky3Finch Therapeutics, Somerville, Massachusetts, USAFinch Therapeutics, Somerville, Massachusetts, USAFinch Therapeutics, Somerville, Massachusetts, USAFinch Therapeutics, Somerville, Massachusetts, USAABSTRACT The gut microbiome plays a key role in bile acid (BA) metabolism, where a diversity of metabolic products contribute to human health and disease. In particular, Inflammatory Bowel Disease (IBD) is characterized by a low concentration of secondary bile acids (SBAs), whose transformation from primary bile acids (PBAs) is an essential function performed solely by gut bacteria. BA-transformation activity mediated by the bile acid inducible (bai) operon has been functionally characterized in the genus Clostridium, and homologous bai gene sequences have been found in metagenome-assembled genomes (MAGs) belonging to other taxa in the human gut, but it is unclear which species of bai-carrying bacteria perform physiologically significant amounts of bile acid transformation in healthy and sick individuals. Here, we analyzed hundreds of stool samples with paired metagenomic and metabolomic data from IBD patients and controls and found that the abundance of the bai operon in metagenomic samples was highly predictive of that sample’s high- or low-SBA metabolic state. We further found that bai genes from the Clostridium species best characterized as BA transformers were more prevalent in IBD patients than in non-IBD controls, while bai genes from uncharacterized taxa known only from MAGs were much more physiologically relevant in non-IBD samples. These un-isolated clades of BA-transforming bacteria merit further research; as beyond their prevalence in the human population, we found some cases in which they engrafted in IBD patients who had undergone fecal microbiota transplantation and experienced a clinical response.IMPORTANCEIn this paper, we identify specific bacteria that perform an important metabolic function in the human gut and demonstrate that in the guts of a large subset of patients with IBD, these bacteria are missing and the function is defective. This is a rare example where the correlation between the absence of specific bacteria and the dysfunction of metabolism is directly observed, not in mice nor in the lab, but in physiologic microbial communities in the human gut. Our results point to a path for studying how a small but important set of bacteria is affected by conditions in the IBD gut and perhaps to the development of interventions to mitigate the loss of these bacteria in IBD.https://journals.asm.org/doi/10.1128/spectrum.01999-24bile acidsbaiFMTIBDdysbiosisgut microbiome |
| spellingShingle | Daniel Peterson Christopher Weidenmaier Sonia Timberlake Rotem Gura Sadovsky Depletion of key gut bacteria predicts disrupted bile acid metabolism in inflammatory bowel disease Microbiology Spectrum bile acids bai FMT IBD dysbiosis gut microbiome |
| title | Depletion of key gut bacteria predicts disrupted bile acid metabolism in inflammatory bowel disease |
| title_full | Depletion of key gut bacteria predicts disrupted bile acid metabolism in inflammatory bowel disease |
| title_fullStr | Depletion of key gut bacteria predicts disrupted bile acid metabolism in inflammatory bowel disease |
| title_full_unstemmed | Depletion of key gut bacteria predicts disrupted bile acid metabolism in inflammatory bowel disease |
| title_short | Depletion of key gut bacteria predicts disrupted bile acid metabolism in inflammatory bowel disease |
| title_sort | depletion of key gut bacteria predicts disrupted bile acid metabolism in inflammatory bowel disease |
| topic | bile acids bai FMT IBD dysbiosis gut microbiome |
| url | https://journals.asm.org/doi/10.1128/spectrum.01999-24 |
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