Udayan Sreeram, Floyd Alexandria N, John Vini, Barrios Bibiana E, Rusconi Brigida A, McDonald Keely G, Schill Ellen Merrick, Kulkarni Devesha H, Martin Andrew L, Gutierrez Rafael, Talati Khushi B, Harris Dalia L, Sundas Sushma, Burgess Kayla M, Pauta Jocelyn T, Joyce Elisabeth L, Wang Jacqueline D, Wilson Leslie D, Knoop Kathryn A, Tarr Phillip I, Hsieh Chyi-Song, Newberry Rodney D
School of Biochemistry and Immunology, Trinity College Dublin, Dublin, Ireland.
Division of Gastroenterology, Department of Internal Medicine, Washington University in Saint Louis School of Medicine, St. Louis, MO, USA.
Nat Microbiol. 2025 Apr;10(4):927-938. doi: 10.1038/s41564-025-01965-1. Epub 2025 Apr 1.
Gut-resident microorganisms have time-limited effects in distant tissues during early life. However, the reasons behind this phenomenon are largely unknown. Here, using bacterial culture techniques, we show that a subset of live gut-resident bacteria translocate and disseminate to extraintestinal tissues (mesenteric lymph nodes and spleen) in preweaning (day of life 17), but not adult (day of life 35), mice. Translocation and dissemination in preweaning mice appeared physiologic as it did not induce an inflammatory response and required host goblet cells, the formation of goblet cell-associated antigen passages, sphingosine-1-phosphate receptor-dependent leukocyte trafficking and phagocytic cells. One translocating strain, Lactobacillus animalis, showed antimicrobial activity against the late-onset sepsis pathogen Escherichia coli ST69 in vitro, and its translocation was associated with protection from systemic sepsis in vivo. While limited in context, these findings challenge the idea that translocation of gut microbiota is pathological and show physiologic and beneficial translocation during early life.
肠道常驻微生物在生命早期对远处组织具有限时效应。然而,这一现象背后的原因很大程度上尚不清楚。在此,我们运用细菌培养技术表明,在断奶前(出生第17天)而非成年(出生第35天)小鼠中,一部分活的肠道常驻细菌会转移并扩散到肠外组织(肠系膜淋巴结和脾脏)。断奶前小鼠中的转移和扩散似乎是生理性的,因为它不会诱导炎症反应,并且需要宿主杯状细胞、杯状细胞相关抗原通道的形成、鞘氨醇-1-磷酸受体依赖性白细胞运输和吞噬细胞。一种转移菌株,即动物乳杆菌,在体外对迟发性败血症病原体大肠杆菌ST69具有抗菌活性,其转移与体内免受全身性败血症的保护作用相关。尽管背景有限,但这些发现挑战了肠道微生物群转移是病理性的观点,并表明在生命早期存在生理性和有益的转移。