The metabolic profile of Bifidobacterium dentium reflects its status as a human gut commensal

Abstract

Background Bifidobacteria are commensal microbes of the mammalian gastrointestinal tract. In this study, we aimed to identify the intestinal colonization mechanisms and key metabolic pathways implemented by Bifidobacterium dentium. Results B. dentium displayed acid resistance, with high viability over a pH range from 4 to 7; findings that correlated to the expression of Na+/H+ antiporters within the B. dentium genome. B. dentium was found to adhere to human MUC2+ mucus and harbor mucin-binding proteins. Using microbial phenotyping microarrays and fully-defined media, we demonstrated that in the absence of glucose, B. dentium could metabolize a variety of nutrient sources. Many of these nutrient sources were plant-based, suggesting that B. dentium can consume dietary substances. In contrast to other bifidobacteria, B. dentium was largely unable to grow on compounds found in human mucus; a finding that was supported by its glycosyl hydrolase (GH) profile. Of the proteins identified in B. dentium by proteomic analysis, a large cohort of proteins were associated with diverse metabolic pathways, indicating metabolic plasticity which supports colonization of the dynamic gastrointestinal environment. Conclusions Taken together, we conclude that B. dentium is well adapted for commensalism in the gastrointestinal tract.

Unraveling the Metabolic Requirements of the Gut Commensal Bacteroides ovatus

“…Proteomic analysis of B. ovatus ATCC 8384 was performed as previously described ( Engevik et al, 2021 ). For all experiments, optima LC/MS-grade acetonitrile (ACN), formic acid (FA), and Promega™ porcine trypsin protease were all purchased from Thermo Fisher Scientific, while ammonium bicarbonate (BioUltra-grade) was purchased from Millipore-Sigma.…”

“…A 100-μL volume of a 10 μg/mL solution of porcine trypsin in 25 mM ammonium bicarbonate was added to the dried proteins and incubated at 37°C for 8 h. Digested samples were chromatographically separated on a Dionex Ultimate 3000 RSLC nano-system (Thermo Scientific) using an Acclaim PepmapTM C-18 capillary column [75 μm (ID) × 150 mm (L), Thermo Scientific] outfitted with an Acclaim PepmapTM C18 trap column [100 μm (ID) × 20 mm (L), Thermo Scientific]. Chromatography was performed as previously described ( Engevik et al, 2020 , 2021 ).…”

“…Samples were analyzed as previously described ( Engevik et al, 2021 ) using an Orbitrap Fusion mass spectrometer (Thermo Scientific) with a nanoionization source operated in positive ion mode using source and global mass spectrometer settings are previously described ( Engevik et al, 2021 ). Resulting data were compared to the Uniprot Bacteroides database (8 Aug 2020) and analyzed using Proteome Discoverer (Thermo Scientific).…”

Mathematical models to study the biology of pathogens and the infectious diseases they cause

“…A literature search and an investigation of transporters in related organisms may reveal the transporter that had been annotated incorrectly. Non-targeted proteomics can be combined with BIOLOG microbial phenotyping microarray-based experiments to detail the metabolic pathways necessary for a gut bacterium such as Bifidobacterium dentium to metabolize dietary sugars typical of the human diet ( Engevik et al., 2021a ).…”

Neurotransmitter Profiles Are Altered in the Gut and Brain of Mice Mono-Associated with Bifidobacterium dentium

“…To address this knowledge gap, we sought to characterize the neuroactive compounds produced by a single human Bifidobacteria species in vitro and in vivo. We selected B. dentium because it is found in infants and adults [53], has the metabolic capacity to colonize the intestine [54], possesses anti-inflammatory, epithelial-barrier enhancing properties [55,56], and stimulates serotonin release from enterochromaffin cells [52]. The importance of these functions in human health motivated us to characterize the neurotransmitter profile of B. dentium.…”