Lactobacillus rhamnosus GG modifies the metabolome of pathobionts in gnotobiotic mice

BMC Microbiology

Amanda Bumber¹  Rajbir Singh²  Sheila Bandyopadhyay²  Iyshwarya Balasubramanian²  Nan Gao²  Lee J. Kerkhof³  Xiaoyang Su⁴  Yuling He⁵  Jinhee Kim⁶  Ian Nadler⁶  Ronaldo P. Ferraris⁶  Danielle Harlan⁶ 

[1] Comparative Medicine Resources, Rutgers University, 07103, Newark, NJ, USA;Department of Biological Sciences, Life Science Center, Rutgers University, 07102, Newark, NJ, USA;Department of Marine and Coastal Sciences, Rutgers University, 71 Dudley Rd, 08901, New Brunswick, NJ, USA;Department of Medicine, Clinical Academic Building, Robert Wood Johnson Medical School, Rutgers University, 08901, New Brunswick, NJ, USA;Department of Medicine, Clinical Academic Building, Robert Wood Johnson Medical School, Rutgers University, 08901, New Brunswick, NJ, USA;Present address: Geriatric Endocrinology Division, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China;Department of Pharmacology, Physiology and Neurosciences, Medical Science Building, New Jersey Medical School, Rutgers University, 07103, Newark, NJ, USA;

关键词: Competitive exclusion;    Fecal metabolites;    Germ-free mice;    Inflammation;    Liquid chromatography, mass spectrometry;    Microbiota;    Propionibacterium acnes;   

DOI  :  10.1186/s12866-021-02178-2

来源: Springer

【 摘 要 】

BackgroundLactobacillus rhamnosus GG (LGG) is the most widely used probiotic, but the mechanisms underlying its beneficial effects remain unresolved. Previous studies typically inoculated LGG in hosts with established gut microbiota, limiting the understanding of specific impacts of LGG on host due to numerous interactions among LGG, commensal microbes, and the host. There has been a scarcity of studies that used gnotobiotic animals to elucidate LGG-host interaction, in particular for gaining specific insights about how it modifies the metabolome. To evaluate whether LGG affects the metabolite output of pathobionts, we inoculated with LGG gnotobiotic mice containing Propionibacterium acnes, Turicibacter sanguinis, and Staphylococcus aureus (PTS).Results16S rRNA sequencing of fecal samples by Ion Torrent and MinION platforms showed colonization of germ-free mice by PTS or by PTS plus LGG (LTS). Although the body weights and feeding rates of mice remained similar between PTS and LTS groups, co-associating LGG with PTS led to a pronounced reduction in abundance of P. acnes in the gut. Addition of LGG or its secretome inhibited P. acnes growth in culture. After optimizing procedures for fecal metabolite extraction and metabolomic liquid chromatography-mass spectrometry analysis, unsupervised and supervised multivariate analyses revealed a distinct separation among fecal metabolites of PTS, LTS, and germ-free groups. Variables-important-in-projection scores showed that LGG colonization robustly diminished guanine, ornitihine, and sorbitol while significantly elevating acetylated amino acids, ribitol, indolelactic acid, and histamine. In addition, carnitine, betaine, and glutamate increased while thymidine, quinic acid and biotin were reduced in both PTS and LTS groups. Furthermore, LGG association reduced intestinal mucosal expression levels of inflammatory cytokines, such as IL-1α, IL-1β and TNF-α.ConclusionsLGG co-association had a negative impact on colonization of P. acnes, and markedly altered the metabolic output and inflammatory response elicited by pathobionts.

【 授权许可】

CC BY