Shmunis School of Biomedicine and Cancer Research, George S. Wise Faculty of Life Sciences, Tel-Aviv University, Tel Aviv, Israel.
Division of Gastroenterology, Rabin Medical Center, Petah-Tikva, Israel.
mBio. 2023 Feb 28;14(1):e0345622. doi: 10.1128/mbio.03456-22. Epub 2023 Jan 31.
Metagenomics has improved our understanding of commensal bacteria that colonize human intestines yet relies almost exclusively on fecal samples. Thus, spatial information about the niche range of these gut microbes and the level of specialized adaptation that they undergo has been inaccessible to fecal metagenomic studies. Here, we leveraged metagenomic data obtained through colonoscopy aspirates from three intestinal sites of healthy adults, and reconstructed metagenome-assembled genomes of several common gut bacteria to address intestinal site-specific evolution. We show that the genomes of bacterial strains at specific intestinal sites are clearly distinct yet are interrelated and are derived from a single founder strain colonizing multiple sites. We also reveal that within those intestinal sites, purifying selection is the dominant evolutionary force acting on Escherichia coli genomes within human hosts. Importantly, no site-specific adaptations at the level of accessory genes were detected, implying that these commensals are well-adapted to several host microniches and can therefore colonize multiple intestinal sites with high efficiency. Nevertheless, bacterial growth rates differ markedly across different sections of the intestine. Metagenomics of aspirate samples can reveal unique strain- and intestinal tissue-specific genomic information. Such information may be critical for understanding bacterial contribution to gastrointestinal diseases, which involve only a part of the intestine, as is often the case in inflammatory bowel disease. By reconstructing bacterial genomes from samples taken from specific sites within the human intestines, via aspiration, we show that strains at specific intestinal sites are genetically distinct yet interrelated and are derived from a single founder population. Organ-specific metagenomic information represents a powerful tool to generate insights into gastrointestinal diseases, which involve only a part of the intestine, such as inflammatory bowel disease.
宏基因组学提高了我们对定植于人类肠道的共生菌的认识，但它几乎完全依赖粪便样本。因此，这些肠道微生物所处生态位的空间信息以及它们经历的专门化适应程度，一直是粪便宏基因组研究无法获得的。在这里，我们利用从健康成年人三个肠道部位的结肠镜抽吸物获得的宏基因组数据，重建了几种常见肠道细菌的宏基因组组装基因组，以解决肠道部位特异性进化问题。我们表明，特定肠道部位的细菌菌株的基因组明显不同，但相互关联，并且源自定植于多个部位的单一创始菌株。我们还揭示了，在这些肠道部位内，在人类宿主内的大肠杆菌基因组中，纯化选择是主要的进化力量。重要的是，没有检测到与附属基因水平相关的特定部位适应，这意味着这些共生菌很好地适应了几个宿主小生境，因此可以高效地定植于多个肠道部位。尽管如此，细菌在不同肠道部位的生长速度存在明显差异。抽吸样本的宏基因组学可以揭示独特的菌株和肠道组织特异性基因组信息。这些信息对于理解细菌对胃肠道疾病的贡献可能至关重要，因为这些疾病仅涉及肠道的一部分，这在炎症性肠病中很常见。通过从人类肠道的特定部位抽吸样本重建细菌基因组，我们表明，特定肠道部位的菌株在遗传上是不同的，但相互关联，并且源自单一创始种群。特定器官的宏基因组信息代表了一种强大的工具，可以深入了解仅涉及肠道一部分的胃肠道疾病，如炎症性肠病。
