Resources to Facilitate Use of the Altered Schaedler Flora (ASF) Mouse Model to Study Microbiome Function

Proctor, Alexandra; Parvinroo, Shadi; Richie, Tanner; Jia, Xinglin; Lee, Sonny T. M.; Karp, Peter D.; Paley, Suzanne M.; Kostić, Aleksandar; Pierre, Joseph F.; Wannemuehler, Michael J.; Phillips, Gregory J

doi:10.1128/msystems.00293-22

Cited by 5 publications

(3 citation statements)

References 109 publications

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“…Since mucosal and systemic immune responses are underdeveloped in GF mice 31 , we next tested the effect of LCWE injection in GF mice raised with altered Schaedler flora (ASF). This well-defined bacterial consortium promotes typical gut structure and immune system development in mice 32,33 . In this model, the severity of LCWE-induced KD vasculitis was significantly decreased compared to SPF mice ( Figure S1G, H ).…”

Section: Resultsmentioning

confidence: 99%

The intestinal microbiota contributes to the development of immune-mediated cardiovascular inflammation and vasculitis in mice

Jena,

Wakita,

Gomez

et al. 2024

Preprint

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SUMMARYAlterations in the intestinal microbiota contribute to the pathogenesis of various cardiovascular disorders, but how they affect the development of Kawasaki disease (KD), an acute pediatric vasculitis, remains unclear. We report that depleting the gut microbiota reduces the development of cardiovascular inflammation in a murine model mimicking KD vasculitis. The development of cardiovascular lesions was associated with alterations in the intestinal microbiota composition and, notably, a decreased abundance ofAkkermansia muciniphilaandFaecalibacterium prausnitzii.Oral supplementation with either of these live or pasteurized individual bacteria, or with short-chain fatty acids (SCFAs) produced by them, attenuated cardiovascular inflammation. Treatment with Amuc_1100, the TLR-2 signaling outer membrane protein fromA. muciniphila, also decreased the severity of vascular inflammation. This study reveals an underappreciated gut microbiota-cardiovascular inflammation axis in KD vasculitis pathogenesis and identifies specific intestinal commensals that regulate vasculitis in mice by producing metabolites or via extracellular proteins acting on gut barrier function.IN BRIEFIt remains unclear whether changes in the intestinal microbiota composition are involved in the development of cardiovascular lesions associated with Kawasaki disease (KD), an immune-mediated vasculitis. Jenaet al.observe alterations in the intestinal microbiota composition of mice developing vasculitis, characterized by reducedA. muciniphilaandF. prausnitzii. Oral supplementation with either of these bacteria, live or pasteurized, or with bacteria-produced short-chain fatty acids (SCFAs) or Amuc_1100, the TLR-2 signaling outer membrane protein ofA. muciniphila, was sufficient to alleviate the development of cardiovascular lesions in mice by promoting intestinal barrier function.HIGHLIGHTSAbsence or depletion of the microbiota decreases the severity of vasculitis in a murine model mimicking KD vasculitis.Supplementation ofB. wadsworthiaandB. fragilispromotes murine KD vasculitis.Decreased abundances ofF. prausnitziiandA. muciniphilaare associated with the development of cardiovascular lesions in mice.Supplementation with either live or pasteurizedA. muciniphilaandF. prausnitzii,or the TLR-2 signaling Amuc_1100, reduces the severity of vasculitis by promoting gut barrier function.

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Section: Resultsmentioning

confidence: 99%

The intestinal microbiota contributes to the development of immune-mediated cardiovascular inflammation and vasculitis in mice

Jena,

Wakita,

Gomez

et al. 2024

Preprint

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“…In contrast to identifying genetic changes associated with host-to-host transmission, we employed a defined microbiota mouse model to establish chronic, long-term colonization of LF82 without requiring re-colonization into new hosts. For this, we introduced LF82 into altered Schaedler flora (ASF) mice, which represent a gnotobiotic animal model where the animals are colonized with only 8 bacterial species, excluding members of the Proteobactericeae 37, 38 . In contrast to conventional mice with a complex microbiota, LF82 can colonize ASF mice at consistent levels without the need for continual reacquisition or disruptive antibiotic treatment 39 .…”

Section: Introductionmentioning

confidence: 99%

TheE. colipathobiont LF82 encodes a unique variant of σ⁷⁰that results in specific gene expression changes and altered phenotypes

Arroyo-Mendoza

Proctor

Correa-Medina

et al. 2023

Preprint

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LF82, an adherent invasiveEscherichia colipathobiont, is associated with Crohn′s disease, an inflammatory bowel disease of unknown etiology. Although LF82 contains no virulence genes, it carries several genetic differences, including single nucleotide polymorphisms (SNPs), that distinguish it from nonpathogenic, commensalE. coli. We have identified and investigated an extremely rare SNP that is within the highly conserved rpoD gene, encoding σ70, the primary sigma factor for RNA polymerase. We demonstrate that this single residue change (D445V) results in specific transcriptome and phenotypic changes that are consistent with multiple phenotypes observed in LF82, including increased antibiotic resistance and biofilm formation, modulation of motility, and increased capacity for methionine biosynthesis. Our work demonstrates that a single residue change within the bacterial primary sigma factor can lead to multiple alterations in gene expression and phenotypic changes, suggesting an underrecognized mechanism by which pathobionts and other strain variants with new phenotypes can emerge.

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“…This study investigates the genomic composition of extracellular vesicles from the Oxford Nanopore Technology long-read genomic DNA sequences of P. goldsteinii strain ASF519 20 . Our study assesses the randomness of the EV-DNA cargo content by examining whether a specific subset of genes consistently exhibits differential abundance compared to that of theoretical random gene packaging.…”

Section: Introductionmentioning

confidence: 99%

DNA characterization reveals potential operon-unit packaging of extracellular vesicle cargo from a gut bacterial symbiont

Cho,

Moore,

Pham

et al. 2023

Preprint

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Extracellular vesicles (EVs) are lipid bilayer-bound entities secreted by cells across all domains of life, known to contain a range of components, including protein complexes, RNA, and DNA. Recent studies on microbial extracellular vesicles indicate that these virus-sized nanoparticles, 40-90nm in diameter, readily cross the epithelial barrier and reach systemic circulation, can be detected in tissues throughout the body in mice and that 1mL of plasma from healthy humans contains up to one million bacterial EVs. They have been recently recognized for their biologically functional roles, including modulation of bacterial physiology and host-microbe interactions, hence their gain in the microbiome research community’s attention. However, the exact understanding of their functionality is still a subject of active research and debate. Here, we employ long-read DNA sequencing on purified extracellular vesicles from a common mammalian gut symbiont, Parabacteroides goldsteinii, to characterize the genomic component within EV cargos. Our findings challenge the notion of DNA packaging into EVs as a stochastic event. Instead, our data demonstrate that the DNA packaging is non-random. Here, we suggest a novel hypothesis of selective EV-DNA packaging, potentially arranged in operon units, hence providing new insights into our understanding of its genetic makeup and its potential role, underlining the importance of our findings in microbial community dynamics.

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Resources to Facilitate Use of the Altered Schaedler Flora (ASF) Mouse Model to Study Microbiome Function

Cited by 5 publications

References 109 publications

The intestinal microbiota contributes to the development of immune-mediated cardiovascular inflammation and vasculitis in mice

The intestinal microbiota contributes to the development of immune-mediated cardiovascular inflammation and vasculitis in mice

TheE. colipathobiont LF82 encodes a unique variant of σ⁷⁰that results in specific gene expression changes and altered phenotypes

DNA characterization reveals potential operon-unit packaging of extracellular vesicle cargo from a gut bacterial symbiont

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Resources to Facilitate Use of the Altered Schaedler Flora (ASF) Mouse Model to Study Microbiome Function

Cited by 5 publications

References 109 publications

The intestinal microbiota contributes to the development of immune-mediated cardiovascular inflammation and vasculitis in mice

The intestinal microbiota contributes to the development of immune-mediated cardiovascular inflammation and vasculitis in mice

TheE. colipathobiont LF82 encodes a unique variant of σ70that results in specific gene expression changes and altered phenotypes

DNA characterization reveals potential operon-unit packaging of extracellular vesicle cargo from a gut bacterial symbiont

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TheE. colipathobiont LF82 encodes a unique variant of σ⁷⁰that results in specific gene expression changes and altered phenotypes