Gut-derived Enterococcus faecium from ulcerative colitis patients promotes colitis in a genetically susceptible mouse host

Seishima, Jun; Iida, Noriho; Kitamura, Kazuya; Yutani, Masahiro; Wang, Ziyu; Seki, Akihiro; Yamashita, Taro; Sakai, Yoshio; Honda, Masao; Kagaya, Takashi; Shirota, Yukihiro; Fujinaga, Yukako; Mizukoshi, Eishiro

doi:10.1186/s13059-019-1879-9

Cited by 89 publications

(66 citation statements)

References 59 publications

(76 reference statements)

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“…Treg-induction) 2,3 and also comprehends SCFAproducing species 46 (Figure 6). Oppositely, an increase in the abundance of oxygen-tolerant pathobionts including E. coli and E. faecium are found to be associated with promoting inflammatory exacerbation ( Figure 6) which consistent with a large body of literature demonstrating that gastrointestinal overgrowth of these species is the hallmark of gastrointestinal dysbiosis and inflammation 47,48 and often associates with adverse clinical outcome 49,50 . Taken together, our data and related computational analyses show that the changes in inflammatory gene expression that accompany treatment of TB is predicted by both the anti-microbial activity of the drugs that lead to pathogen clearance and by antibiotic induced changes in microbiome composition.…”

Section: Longitudinal Profiling In An Early Bactericidal Activity Hrzsupporting

confidence: 81%

Intestinal microbiome composition influences the peripheral inflammatory state during treatment of human tuberculosis

Wipperman¹,

Bhattarai²,

Vorkas³

et al. 2020

Preprint

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Although the composition of the intestinal microbiota influences systemic immune responses, the contribution of this relationship to infectious disease pathogenesis and to the resolution of infectious diseases by antibiotic therapy is poorly understood. This question is rarely examined in humans due to the difficulty in dissociating the immunologic effects of antibiotic-induced pathogen clearance and salutary microbiome alteration. To address these questions in the context of Tuberculosis, we analyzed three independent human datasets from Haiti (two longitudinal treatment and one cross-sectional control), a prototypical infection remarkable for chronic inflammation, in which we had measured sputum TB bacterial load, gut microbiota composition, and peripheral blood transcriptomics. Using data from the longitudinal datasets combined with inflammatory pathway enrichment analysis, we determined that antibiotic treatment of TB, despite significantly perturbing the gut microbiota, dampens the proinflammatory signature characteristic of active TB. Contrarily, an investigational TB treatment that failed to clear TB, but that caused similar microbiota perturbations, exacerbated peripheral inflammation. To decouple the effects of antibiotic induced changes in the microbiota from Mtb sterilization as predictors of normalization of TB associated inflammation, we applied random forest regression to the microbiome-transcriptome-sputum data from the two longitudinal datasets. We found inflammatory renormalization is positively affected by both pathogen sterilization and by the abundance of health-associated Cluster IV and Cluster XIa Clostridia. Oppositely, increases in the abundance of commonly known pathobionts such as Bacilli and Proteobacteria clusters predict inflammatory exacerbation. We independently investigated and validated these microbiota-peripheral inflammatory signature associations by applying machine learning to the peripheral gene expression and microbiota profiling in an independent human cohort of 52 healthy control individuals. Together, our findings indicate that antibiotic-induced reduction in pathogen burden and changes in the microbiome are independently associated with treatment-induced changes of the inflammatory response of active TB, and more broadly indicate that response to antibiotic therapy may be a combined effect of pathogen killing and microbiome driven immunomodulation. Our results provide support to the hypothesis that there exists clear links between microbiome composition and host peripheral gene expression in humans that can be biologically elucidated using common and well validated molecular pathway analyses.

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Section: Longitudinal Profiling In An Early Bactericidal Activity Hrzsupporting

confidence: 81%

Intestinal microbiome composition influences the peripheral inflammatory state during treatment of human tuberculosis

Wipperman¹,

Bhattarai²,

Vorkas³

et al. 2020

Preprint

View full text Add to dashboard Cite

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“…We did not find any literature data correlating the abundance of this genus with ulcerative colitis. However, Collinsella was found at lower frequencies in children and adults with UC and Crohn’s disease (CD) [ 65 , 66 ], and in patients with irritable bowel syndrome [ 67 ]. A significant decrease in the family Coriobacteriaceae was observed in stool samples from patients with CD [ 68 ], however, some authors consider Collinsella to be a pathobiont because its occurrence has been associated with type 2 diabetes [ 69 ], the progression of insulin resistance during pregnancy [ 70 ], rheumatoid arthritis [ 71 ], and cholesterol metabolism [ 72 ].…”

Section: Discussionmentioning

confidence: 99%

Gut Microbiome Changes in Patients with Active Left-Sided Ulcerative Colitis after Fecal Microbiome Transplantation and Topical 5-aminosalicylic Acid Therapy

Schierová

Březina

Mrázek

et al. 2020

Cells

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Ulcerative colitis (UC) is an inflammatory bowel disease, and intestinal bacteria are implicated in the pathogenesis of this disorder. The administration of aminosalicylates (5-ASA) is a conventional treatment that targets the mucosa, while fecal microbial transplantation (FMT) is a novel treatment that directly targets the gut microbiota. The aim of this study was to identify changes in fecal bacterial composition after both types of treatments and evaluate clinical responses. Sixteen patients with active left-sided UC underwent enema treatment using 5-ASA (n = 8) or FMT (n = 8) with a stool from a single donor. Fecal microbiota were analyzed by 16S rDNA high-throughput sequencing, and clinical indices were used to assess the efficacy of treatments. 5-ASA therapy resulted in clinical remission in 50% (4/8) of patients, but no correlation with changes in fecal bacteria was observed. In FMT, remission was achieved in 37.5% (3/8) of patients and was associated with a significantly increased relative abundance of the families Lachnospiraceae, Ruminococcaceae, and Clostridiaceae of the phylum Firmicutes, and Bifidobacteriaceae and Coriobacteriaceae of the phylum Actinobacteria. At the genus level, Faecalibacterium, Blautia, Coriobacteria, Collinsela, Slackia, and Bifidobacterium were significantly more frequent in patients who reached clinical remission. However, the increased abundance of beneficial taxa was not a sufficient factor to achieve clinical improvement in all UC patients. Nevertheless, our preliminary results indicate that FMT as non-drug-using method is thought to be a promising treatment for UC patients.

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“…After 15 days of infection, the pre-extracted DNA of fecal samples were divided into two groups based on whether the corresponding mice died or survived from the infection. Then, qRT-PCR was performed to detect B. pseudolongum and B. animalis as previously described [57]. Briefly, 2 ng of fecal DNA was amplified with SYBR Green (Roche) and primers B_plon-f/r or B_ani-f/r to detect B. pseudolongum or B. animalis, respectively [58].…”

Section: Qrt-pcrmentioning

confidence: 99%

Influenza infection elicits an expansion of gut population of endogenous Bifidobacterium animalis which protects mice against infection

Zhang

Feng

et al. 2020

Genome Biol

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Background: Influenza is a severe respiratory illness that continually threatens global health. It has been widely known that gut microbiota modulates the host response to protect against influenza infection, but mechanistic details remain largely unknown. Here, we took advantage of the phenomenon of lethal dose 50 (LD 50) and metagenomic sequencing analysis to identify specific anti-influenza gut microbes and analyze the underlying mechanism. Results: Transferring fecal microbes from mice that survive virulent influenza H7N9 infection into antibiotic-treated mice confers resistance to infection. Some gut microbes exhibit differential features to lethal influenza infection depending on the infection outcome. Bifidobacterium pseudolongum and Bifidobacterium animalis levels are significantly elevated in surviving mice when compared to dead or mockinfected mice. Oral administration of B. animalis alone or the combination of both significantly reduces the severity of H7N9 infection in both antibiotic-treated and germ-free mice. Functional metagenomic analysis suggests that B. animalis mediates the anti-influenza effect via several specific metabolic molecules. In vivo tests confirm valine and coenzyme A produce an anti-influenza effect. Conclusions: These findings show that the severity of influenza infection is closely related to the heterogeneous responses of the gut microbiota. We demonstrate the anti-influenza effect of B. animalis, and also find that the gut population of endogenous B. animalis can expand to enhance host influenza resistance when lethal influenza infection occurs, representing a novel interaction between host and gut microbiota. Further, our data suggest the potential utility of Bifidobacterium in the prevention and as a prognostic predictor of influenza.

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Gut-derived Enterococcus faecium from ulcerative colitis patients promotes colitis in a genetically susceptible mouse host

Cited by 89 publications

References 59 publications

Intestinal microbiome composition influences the peripheral inflammatory state during treatment of human tuberculosis

Intestinal microbiome composition influences the peripheral inflammatory state during treatment of human tuberculosis

Gut Microbiome Changes in Patients with Active Left-Sided Ulcerative Colitis after Fecal Microbiome Transplantation and Topical 5-aminosalicylic Acid Therapy

Influenza infection elicits an expansion of gut population of endogenous Bifidobacterium animalis which protects mice against infection

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