Microbes with higher metabolic independence are enriched in human gut microbiomes under stress

Veseli, Iva; Chen, Yiqun T.; Schechter, Matthew S.; Vanni, Chiara; Fogarty, Emily C.; Watson, Andrea R.; Jabrì, Bana; Blekhman, Ran; Willis, Amy; Yu, Michael; Fernàndez-Guerra, Antonio; Fuessel, Jessika; Eren, A. Murat

doi:10.1101/2023.05.10.540289

Cited by 11 publications

(8 citation statements)

References 123 publications

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“…66,67 Our data support the hypothesis that auxotrophic bacteria such as RF39 are less likely to survive harsh colitic environments, as has been suggested to occur in IBD patients. 68,69 In contrast, Group 2 bacterial taxa Erysipelatoclostridium and E. fissicatena persistently increase after colitis development, as reported elsewhere. 70–87 While the mechanisms behind this increase are unclear, our data align with the literature while also contributing a finer time scale regarding their changes in abundance during colitis.…”

Section: Discussionsupporting

confidence: 78%

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Dextran sodium sulfate-induced colitis alters the proportion and composition of replicating gut bacteria

Beauchemin,

Hunter,

Maurice

2024

Preprint

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The bacteria living in the human gut are essential for host health. Though the composition and metabolism of these bacteria is well described in both healthy hosts and those with intestinal disease, less is known about the activity of the gut bacteria prior to, and during, disease development, especially regarding gut bacterial replication. Here, we use a recently developed single-cell technique alongside existing metagenomics-based tools to identify, track, and quantify the replicating gut bacteria and their replication dynamics in the dextran sodium sulfate mouse model of colitis. We show that the proportion of replicating gut bacteria decreases when mice have the highest levels of inflammation and returns to baseline levels as mice begin recovering. We additionally report significant alterations in the composition of the total replicating gut bacterial community during colitis development. On the taxa level, we observe significant changes in the abundance of taxa such as the mucus-degrading Akkermansia muciniphila and the poorly described Erysipelatoclostridium genus. We further demonstrate that many taxa exhibit variable replication rates during colitis, including A. muciniphila. Lastly, we show that colitis development is positively correlated with increases in the presence and abundance of bacteria predicted to be fast replicators, suggesting that taxa with the potential to replicate quickly may have an advantage during intestinal inflammation. These data support the need for additional research using activity-based approaches to further characterize the gut bacterial response to intestinal inflammation and its consequences for both the host and the gut microbial community at large.

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Section: Discussionsupporting

confidence: 78%

“…66,67 Our data support the hypothesis that auxotrophic bacteria such as RF39 are less likely to survive harsh colitic environments, as has been suggested to occur in IBD patients. 68,69…”

Section: Discussionmentioning

confidence: 99%

Dextran sodium sulfate-induced colitis alters the proportion and composition of replicating gut bacteria

Beauchemin,

Hunter,

Maurice

2024

Preprint

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“…DC was undetectable in the stool of patient 207 ( 74 ) when B. fragilis P207 bloomed to become the dominant species in the pouch ( 24 ). Thus, it is reasonable to conclude that the absence of deoxycholate contributed, at least in part, to the population expansion of B. fragilis in patient 207, though other factors relating to the overall metabolic versatility of B. fragilis ( 75 , 76 ) likely contributed to its bloom as well.…”

Section: Discussionmentioning

confidence: 99%

Bile acid fitness determinants of a Bacteroides fragilis isolate from a human pouchitis patient

Fiebig,

Schnizlein,

Pena-Rivera

et al. 2024

mBio

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Bacteroides fragilis comprises 1%–5% of the gut microbiota in healthy humans but can expand to >50% of the population in ulcerative colitis (UC) patients experiencing inflammation. The mechanisms underlying such microbial blooms are poorly understood, but the gut of UC patients has physicochemical features that differ from healthy patients and likely impact microbial physiology. For example, levels of the secondary bile acid deoxycholate (DC) are highly reduced in the ileoanal J-pouch of UC colectomy patients. We isolated a B. fragilis strain from a UC patient with pouch inflammation (i.e., pouchitis) and developed it as a genetic model system to identify genes and pathways that are regulated by DC and that impact B. fragilis fitness in DC and crude bile. Treatment of B. fragilis with a physiologically relevant concentration of DC reduced cell growth and remodeled transcription of one-quarter of the genome. DC strongly induced expression of chaperones and select transcriptional regulators and efflux systems, and down-regulated protein synthesis genes. Using a barcoded collection of ≈50,000 unique insertional mutants, we further defined B. fragilis genes that contribute to fitness in media containing DC or crude bile. Genes impacting cell envelope functions including cardiolipin synthesis, cell surface glycosylation, and systems implicated in sodium-dependent bioenergetics were major bile acid fitness factors. As expected, there was limited overlap between transcriptionally regulated genes and genes that impacted fitness in bile when disrupted. Our study provides a genome-scale view of a B. fragilis bile response and genetic determinants of its fitness in DC and crude bile. IMPORTANCE The Gram-negative bacterium Bacteroides fragilis is a common member of the human gut microbiota that colonizes multiple host niches and can influence human physiology through a variety of mechanisms. Identification of genes that enable B. fragilis to grow across a range of host environments has been impeded in part by the relatively limited genetic tractability of this species. We have developed a high-throughput genetic resource for a B. fragilis strain isolated from a UC pouchitis patient. Bile acids limit microbial growth and are altered in abundance in UC pouches, where B. fragilis often blooms. Using this resource, we uncovered pathways and processes that impact B. fragilis fitness in bile and that may contribute to population expansions during bouts of gut inflammation.

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“…Pseudofinder v1.1.0 [ 41 ] and DefenseFinder [ 42 ] were used to identify the proportion of pseudogenes and number of antiviral defence systems in all Erwinia genomes. To compare metabolic profiles between Erwinia genomes in the pangenome database, anvi’o was used with the programmes anvi-run-kegg-kofams and anvi-estimate-metabolism , which utilised previous annotation of genes with KEGG orthologs (KOs) [ 43 ]. The outputted completeness matrix for amino acid, lipid, carbohydrate, and vitamin metabolic pathways was then inputted into pHeatmap v1.0.12 [ 44 ] and visualised using RStudio.…”

Section: Methodsmentioning

confidence: 99%

Comparative genomics of a novel Erwinia species associated with the Highland midge (Culicoides impunctatus)

Pilgrim

2024

Microbial Genomics

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Erwinia (Enterobacterales: Erwiniaceae) are a group of cosmopolitan bacteria best known as the causative agents of various plant diseases. However, other species in this genus have been found to play important roles as insect endosymbionts supplementing the diet of their hosts. Here, I describe Candidatus Erwinia impunctatus (Erwimp) associated with the Highland midge Culicoides impunctatus (Diptera: Ceratopogonidae), an abundant biting pest in the Scottish Highlands. The genome of this new Erwinia species was assembled using hybrid long and short read techniques, and a comparative analysis was undertaken with other members of the genus to understand its potential ecological niche and impact. Genome composition analysis revealed that Erwimp is similar to other endophytic and ectophytic species in the genus and is unlikely to be restricted to its insect host. Evidence for an additional plant host includes the presence of a carotenoid synthesis operon implicated as a virulence factor in plant-associated members in the sister genus Pantoea. Unique features of Erwimp include several copies of intimin-like proteins which, along with signs of genome pseudogenization and a loss of certain metabolic pathways, suggests an element of host restriction seen elsewhere in the genus. Furthermore, a screening of individuals over two field seasons revealed the absence of the bacteria in Culicoides impunctatus during the second year indicating this microbe-insect interaction is likely to be transient. These data suggest that Culicoides impunctatus may have an important role to play beyond a biting nuisance, as an insect vector transmitting Erwimp alongside any conferred impacts to surrounding biota.

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Microbes with higher metabolic independence are enriched in human gut microbiomes under stress

Cited by 11 publications

References 123 publications

Dextran sodium sulfate-induced colitis alters the proportion and composition of replicating gut bacteria

Dextran sodium sulfate-induced colitis alters the proportion and composition of replicating gut bacteria

Bile acid fitness determinants of a Bacteroides fragilis isolate from a human pouchitis patient

Comparative genomics of a novel Erwinia species associated with the Highland midge (Culicoides impunctatus)

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