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1. Metabolic Feedback Inhibition Influences Metabolite Secretion by the Human Gut Symbiont Bacteroides thetaiotaomicron

   https://doi.org/10.1128/mSystems.00252-20  

   Catlett, Jennie L.; Catazaro, Jonathan; Cashman, Mikaela; Carr, Sean; Powers, Robert; Cohen, Myra B.; Buan, Nicole R. (October 2020, mSystems)

   Lal, Rup (Ed.)

   ABSTRACT Microbial metabolism and trophic interactions between microbes give rise to complex multispecies communities in microbe-host systems. Bacteroides thetaiotaomicron ( B. theta ) is a human gut symbiont thought to play an important role in maintaining host health. Untargeted nuclear magnetic resonance metabolomics revealed B. theta secretes specific organic acids and amino acids in defined minimal medium. Physiological concentrations of acetate and formate found in the human intestinal tract were shown to cause dose-dependent changes in secretion of metabolites known to play roles in host nutrition and pathogenesis. While secretion fluxes varied, biomass yield was unchanged, suggesting feedback inhibition does not affect metabolic bioenergetics but instead redirects carbon and energy to CO 2 and H 2 . Flux balance analysis modeling showed increased flux through CO 2 -producing reactions under glucose-limiting growth conditions. The metabolic dynamics observed for B. theta , a keystone symbiont organism, underscores the need for metabolic modeling to complement genomic predictions of microbial metabolism to infer mechanisms of microbe-microbe and microbe-host interactions. IMPORTANCE Bacteroides is a highly abundant taxon in the human gut, and Bacteroides thetaiotaomicron ( B. theta ) is a ubiquitous human symbiont that colonizes the host early in development and persists throughout its life span. The phenotypic plasticity of keystone organisms such as B. theta is important to understand in order to predict phenotype(s) and metabolic interactions under changing nutrient conditions such as those that occur in complex gut communities. Our study shows B. theta prioritizes energy conservation and suppresses secretion of “overflow metabolites” such as organic acids and amino acids when concentrations of acetate are high. Secreted metabolites, especially amino acids, can be a source of nutrients or signals for the host or other microbes in the community. Our study suggests that when metabolically stressed by acetate, B. theta stops sharing with its ecological partners. 

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2. Determinants of raffinose family oligosaccharide use in Bacteroides species

   https://doi.org/10.1128/jb.00235-24  

   Basu, Anubhav; Adams, Amanda_N D; Degnan, Patrick H; Vanderpool, Carin K (October 2024, Journal of Bacteriology)

   O'Toole, George (Ed.)

   ABSTRACT Bacteroidesspecies are successful colonizers of the human colon and can utilize a wide variety of complex polysaccharides and oligosaccharides that are indigestible by the host. To do this, they use enzymes encoded in polysaccharide utilization loci (PULs). While recent work has uncovered the PULs required for the use of some polysaccharides, howBacteroidesutilize smaller oligosaccharides is less well studied. Raffinose family oligosaccharides (RFOs) are abundant in plants, especially legumes, and consist of variable units of galactose linked by α-1,6 bonds to a sucrose (glucose α-1-β-2 fructose) moiety. Previous work showed that an α-galactosidase, BT1871, is required for RFO utilization inBacteroides thetaiotaomicron. Here, we identify two different types of mutations that increaseBT1871mRNA levels and improveB. thetaiotaomicrongrowth on RFOs. First, a novel spontaneous duplication ofBT1872andBT1871places these genes under the control of a ribosomal promoter, driving highBT1871transcription. Second, nonsense mutations in a gene encoding the PUL24 anti-sigma factor likewise increaseBT1871transcription. We then show that hydrolases from PUL22 work together with BT1871 to break down the sucrose moiety of RFOs and determine that the master regulator of carbohydrate utilization (BT4338) plays a role in RFO utilization inB. thetaiotaomicron. Examining the genomes of otherBacteroidesspecies, we found homologs of BT1871 in a subset and showed that representative strains of species with a BT1871 homolog grew better on melibiose than species that lack a BT1871 homolog. Altogether, our findings shed light on how an important gut commensal utilizes an abundant dietary oligosaccharide. IMPORTANCEThe gut microbiome is important in health and disease. The diverse and densely populated environment of the gut makes competition for resources fierce. Hence, it is important to study the strategies employed by microbes for resource usage. Raffinose family oligosaccharides are abundant in plants and are a major source of nutrition for the microbiota in the colon since they remain undigested by the host. Here, we study how the model commensal organism,Bacteroides thetaiotaomicronutilizes raffinose family oligosaccharides. This work highlights how an important member of the microbiota uses an abundant dietary resource. 

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3. Understanding the factors regulating host–microbiome interactions using Caenorhabditis elegans

   https://doi.org/10.1098/rstb.2023.0059  

   Singh, Anupama; Luallen, Robert J (May 2024, Philosophical Transactions of the Royal Society B: Biological Sciences)

   The Human Microbiome Project was a research programme that successfully identified associations between microbial species and healthy or diseased individuals. However, a major challenge identified was the absence of model systems for studying host–microbiome interactions, which would increase our capacity to uncover molecular interactions, understand organ-specificity and discover new microbiome-altering health interventions.Caenorhabditis eleganshas been a pioneering model organism for over 70 years but was largely studied in the absence of a microbiome. Recently, ecological sampling of wild nematodes has uncovered a large amount of natural genetic diversity as well as a slew of associated microbiota. The field has now explored the interactions ofC. eleganswith its associated gut microbiome, a defined and non-random microbial community, highlighting its suitability for dissecting host–microbiome interactions. This core microbiome is being used to study the impact of host genetics, age and stressors on microbiome composition. Furthermore, single microbiome species are being used to dissect molecular interactions between microbes and the animal gut. Being amenable to health altering genetic and non-genetic interventions,C. eleganshas emerged as a promising system to generate and test new hypotheses regarding host–microbiome interactions, with the potential to uncover novel paradigms relevant to other systems. This article is part of the theme issue ‘Sculpting the microbiome: how host factors determine and respond to microbial colonization’. 

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4. Probing interspecies metabolic interactions within a synthetic binary microbiome using genome-scale modeling

   https://doi.org/10.20517/mrr.2023.70  

   Badr, Kiumars; He, Q Peter; Wang, Jin (May 2024, Microbiome Research Reports)

   Aim: Metabolic interactions within a microbial community play a key role in determining the structure, function, and composition of the community. However, due to the complexity and intractability of natural microbiomes, limited knowledge is available on interspecies interactions within a community. In this work, using a binary synthetic microbiome, a methanotroph-photoautotroph (M-P) coculture, as the model system, we examined different genome-scale metabolic modeling (GEM) approaches to gain a better understanding of the metabolic interactions within the coculture, how they contribute to the enhanced growth observed in the coculture, and how they evolve over time. Methods: Using batch growth data of the model M-P coculture, we compared three GEM approaches for microbial communities. Two of the methods are existing approaches: SteadyCom, a steady state GEM, and dynamic flux balance analysis (DFBA) Lab, a dynamic GEM. We also proposed an improved dynamic GEM approach, DynamiCom, for the M-P coculture. Results: SteadyCom can predict the metabolic interactions within the coculture but not their dynamic evolutions; DFBA Lab can predict the dynamics of the coculture but cannot identify interspecies interactions. DynamiCom was able to identify the cross-fed metabolite within the coculture, as well as predict the evolution of the interspecies interactions over time. Conclusion: A new dynamic GEM approach, DynamiCom, was developed for a model M-P coculture. Constrained by the predictions from a validated kinetic model, DynamiCom consistently predicted the top metabolites being exchanged in the M-P coculture, as well as the establishment of the mutualistic N-exchange between the methanotroph and cyanobacteria. The interspecies interactions and their dynamic evolution predicted by DynamiCom are supported by ample evidence in the literature on methanotroph, cyanobacteria, and other cyanobacteria-heterotroph cocultures. 

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5. The gut bacterial microbiome of the Threeridge mussel, Amblema plicata , varies between rivers but shows a consistent core community

   https://doi.org/10.1111/fwb.13905  

   Lawson, Lauren A.; Atkinson, Carla L.; Jackson, Colin R. (March 2022, Freshwater Biology)

   Abstract Freshwater mussels are important for nutrient cycling and ecosystem health as they filter feed on their surrounding water. This filter feeding makes these bivalves especially sensitive to conditions in their environment. Gut microbial communities (microbiomes) have been recognised as important to both host organism and ecosystem health; however, how freshwater mussel microbiomes are organised and influenced is unclear.In this study, the gut bacterial microbiome of Threeridge mussel,Amblema plicata, was compared across two river basins, five rivers, and nine local sites in the south‐eastern U.S.A. Mussel gut tissue was dissected, DNA extracted, and the microbiome characterised by high throughput sequencing of the V4 region of the 16S ribosomal RNA gene.Planctomycetes, Firmicutes, and Cyanobacteria were the most common bacterial phyla within the guts of all sampledA.plicata. However, the relative abundances of these major bacterial phyla differed between mussels sampled from different rivers and river basins, as did the relative abundance of specific bacterial operational taxonomic units (OTUs). Despite these differences, a core microbiome was identified across all mussels, with eight OTUs being consistent members of theA.plicatamicrobiome at all sites, the most abundant OTU identifying as a member of the family Planctomycetaceae. Geographic distance between sites was not correlated with similarity in the structure of the gut microbiome, which was more related to site physicochemistry.Overall, these results suggest that while physicochemical conditions affect the composition of transient bacteria in the Threeridge mussel gut microbiome, the core microbiome is largely unaffected, and a portion of theA.plicatamicrobiome is retained regardless of the river system.How long transient bacteria remain in the gut, and to what extent these transient microbes aid in host function is still unknown. Core microbiota have been found to aid in multiple functions within animal hosts, and within freshwater mussels this core microbiome may aid in nutrient processing and cycling. Therefore, it is important to look at both transient and core microbes when studying the structure of freshwater invertebrate microbiomes. 

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