Gut microbiota strain richness is species specific and affects engraftment

• 成果类型: Article
• 署名作者: Chen-Liaw, Alice; Aggarwala, Varun; Mogno, Ilaria; Haifer, Craig; Li, Zhihua; Eggers, Joseph; Helmus, Drew; Hart, Amy; Wehkamp, Jan; Lamouse-Smith, Esi S. N.; Kerby, Robert L.; Rey, Federico E.; Colombel, Jean Frederic; Kamm, Michael A.; Olle, Bernat; Norman, Jason M.; Menon, Rajita; Watson, Andrea R.; Crossett, Emily; Terveer, Elisabeth M.; Keller, Josbert J.; Borody, Thomas J.; Grinspan, Ari; Paramsothy, Sudarshan; Kaakoush, Nadeem O.; Dubinsky, Marla C.; Faith, Jeremiah J.
• 署名单位: Icahn School of Medicine at Mount Sinai; Icahn School of Medicine at Mount Sinai; University of Sydney; University of New South Wales Sydney; Icahn School of Medicine at Mount Sinai; Johnson & Johnson; Janssen Pharmaceuticals; University of Wisconsin System; University of Wisconsin Madison; NSW Health; St Vincents Hospital Sydney; St Vincent's Health; St Vincent's Hospital Melbourne; Leiden University - Excl LUMC; Leiden University; Leiden University Medical Center (LUMC); Leiden University; Leiden University Medical Center (LUMC); Leiden University - Excl LUMC; Haaglanden Medical Center; Leiden University - Excl LUMC; Leiden University; Leiden University Medical Center (LUMC); Centre For Digestive Diseases; Macquarie University; University of New South Wales Sydney
• 刊物名称: Nature
• ISSN/ISSBN: 0028-0917
• DOI: 10.1038/s41586-024-08242-x
• 发表日期: 2025-01-09
• 页码: 422-+
• 关键词: clostridium-difficile; population-structure; diversity; reveals; transplantation; transmission; landscape; EVOLUTION; colitis

摘要

Despite the fundamental role of bacterial strain variation in gut microbiota function(1-6), the number of unique strains of a species that can stably colonize the human intestine is still unknown for almost all species. Here we determine the strain richness (SR) of common gut species using thousands of sequenced bacterial isolates with paired metagenomes. We show that SR varies across species, is transferable by faecal microbiota transplantation, and is uniquely low in the gut compared with soil and lake environments. Active therapeutic administration of supraphysiologic numbers of strains per species increases recipient SR, which then converges back to the population average after dosing is ceased. Stratifying engraftment outcomes by high or low SR shows that SR predicts microbial addition or replacement in faecal transplants. Together, these results indicate that properties of the gut ecosystem govern the number of strains of each species colonizing the gut and thereby influence strain addition and replacement in faecal microbiota transplantation and defined live biotherapeutic products.