Laboratory of Gastrointestinal Microbiology, Jiangsu Key Laboratory of Gastrointestinal Nutrition and Animal Health, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, 210095, China.
National Center for International Research on Animal Gut Nutrition, Nanjing Agricultural University, Nanjing, 210095, China.
ISME J. 2022 Nov;16(11):2491-2502. doi: 10.1038/s41396-022-01287-8. Epub 2022 Jul 27.
The mammalian intestine harbors heterogeneous distribution of microbes among which specific taxa (e.g. Lactobacillus) dominate across mammals. Deterministic factors such as nutrient availability and utilization may affect microbial distributions. Due to physiological complexity, mechanisms linking nutrient utilization and the dominance of key taxa remain unclear. Lactobacillus amylovorus is a predominant species in the small intestine of pigs. Employing a pig model, we found that the small intestine was dominated by Lactobacillus and particularly L. amylovorus, and enriched with peptide-bound amino acids (PBAAs), all of which were further boosted after a peptide-rich diet. To investigate the bacterial growth dominance mechanism, a representative strain L. amylovorus S1 was isolated from the small intestine and anaerobically cultured in media with free amino acids or peptides as sole nitrogen sources. L. amylovorus S1 grew preferentially with peptide-rich rather than amino acid-rich substrates, as reflected by enhanced growth and PBAA utilization, and peptide transporter upregulations. Utilization of free amino acids (e.g. methionine, valine, lysine) and expressions of transporters and metabolic enzymes were enhanced simultaneously in peptide-rich substrate. Additionally, lactate was elevated in peptide-rich substrates while acetate in amino acid-rich substrates, indicating distinct metabolic patterns depending on substrate forms. These results suggest that an increased capability of utilizing PBAAs contributes to the dominance of L. amylovorus, indicating amino acid utilization as a deterministic factor affecting intestinal microbial distribution. These findings may provide new insights into the microbe-gut nutrition interplay and guidelines for dietary manipulations toward gut health especially small intestine health.
哺乳动物的肠道内存在着微生物的异质分布,其中特定的分类群(如乳酸杆菌)在哺乳动物中占据主导地位。确定因素,如营养物质的可用性和利用,可能会影响微生物的分布。由于生理复杂性,将营养物质利用与关键分类群的主导地位联系起来的机制仍不清楚。乳酸杆菌属是猪小肠中的主要物种。在猪模型中,我们发现小肠被乳酸杆菌属主导,特别是被 L. amylovorus 主导,并且富含肽结合氨基酸(PBAAs),所有这些在富含肽的饮食后都进一步增加。为了研究细菌生长优势的机制,我们从小肠中分离出一个代表菌株 L. amylovorus S1,并在含有游离氨基酸或肽作为唯一氮源的培养基中进行厌氧培养。L. amylovorus S1 更喜欢利用富含肽的而不是富含氨基酸的底物,这反映在增强的生长和 PBAAs 利用以及肽转运体的上调。在富含肽的底物中,游离氨基酸(如蛋氨酸、缬氨酸、赖氨酸)的利用和转运体及代谢酶的表达同时增强。此外,在富含肽的底物中乳酸升高,而在富含氨基酸的底物中乙酸升高,这表明根据底物形式存在不同的代谢模式。这些结果表明,增加利用 PBAAs 的能力有助于 L. amylovorus 的优势,表明氨基酸利用是影响肠道微生物分布的确定因素。这些发现可能为微生物-肠道营养相互作用提供新的见解,并为饮食干预以促进肠道健康,特别是小肠健康提供指导。