Oral administration of <i>Parabacteroides distasonis</i> antigens attenuates experimental murine colitis through modulation of immunity and microbiota composition

Kverka, Miloslav; Zákostelská, Zuzana Jirásková; Klimešová, Klára; Sokol, D.; Hudcovic, Tomáš; Hrncírová, L; Rossmann, P; Mrázek, Jakub; Kopečný, J.; Verdú, Elena F.; Tlaskalová‐Hogenová, Helena

doi:10.1111/j.1365-2249.2010.04286.x

Cited by 281 publications

(280 citation statements)

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“…In human biopsies, P. distasonis was significantly more abundant in uninflamed versus inflamed tissue (Zitomersky et al, 2013). Consistent with this observation, oral administration of P. distasonis antigens attenuates intestinal inflammation during colitis in mice (Kverka et al, 2011).…”

Section: Taxonomic Associations With Fungal-induced Cytokine Responsessupporting

confidence: 71%

Linking the Human Gut Microbiome to Inflammatory Cytokine Production Capacity

Schirmer¹,

Smeekens²,

Vlamakis³

et al. 2016

Cell

230

196

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SummaryGut microbial dysbioses are linked to aberrant immune responses, which are often accompanied by abnormal production of inflammatory cytokines. As part of the Human Functional Genomics * Correspondence: xavier@molbio.mgh.harvard.edu (R.J.X.), mihai.netea@radboudumc.nl (M.G.N.). Lead ContactPublisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Author ContributionsMS performed the metagenomics data analyses and correlation analyses. SPS, MJ, MO, AK, and MJB performed the immunological assays and processed and analyzed the data. MS, HV, EAF, CH, MGN, and RJX interpreted the results. MS, EAF, and CH led the computational methods and research development. SPS, MJ, and MO collected clinical samples. SPS, TJ, and LJ performed functional validation experiments. MS, SPS, HV, CH, MGN, and RJX assembled and wrote the paper. MS, HV, MGN, and RJX served as project leaders. JF, AZ, LABJ, CW, MGN, and RJX designed the cohort study. CH, CW, MGN, and RJX served as principal investigators. Table S1. Related to Figure 3. Correlation coefficients for all significant species associations Table S2. Related to Figure 3. FDR values for all significant species associations Table S3. Related to Figure 3. Correlation coefficients for all significant genus associations Table S4. Related to Figure 3. FDR values for all significant genus associations Table S5. Related to Figure 4. Correlation coefficients for all significant pathway associations Table S6. Related to Figure 4. FDR values for all significant pathway associations Table S7. Related to Figure 4. Correlation coefficients for all significant GO category associations Table S8. Related to Figure 4. FDR values for all significant GO category associations HHS Public Access Author Manuscript Author ManuscriptAuthor Manuscript Author ManuscriptProject (HFGP), we investigate how differences in composition and function of gut microbial communities may contribute to inter-individual variation in cytokine responses to microbial stimulations in healthy humans. We observe microbiome-cytokine interaction patterns that are stimulus-specific, cytokine-specific, and cytokine-and stimulus-specific. Validation of two predicted host-microbial interactions reveal that TNFα and IFNγ production are associated with specific microbial metabolic pathways: palmitoleic acid metabolism and tryptophan degradation to tryptophol. Besides providing a resource of predicted microbially-derived mediators that influence immune phenotypes in response to common microorganisms, these data can help to define principles for understanding disease susceptibility. The three HFGP stud...

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Section: Taxonomic Associations With Fungal-induced Cytokine Responsessupporting

confidence: 71%

Linking the Human Gut Microbiome to Inflammatory Cytokine Production Capacity

Schirmer¹,

Smeekens²,

Vlamakis³

et al. 2016

Cell

230

196

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“…In addition, our result shows a much higher increase of the P. distasonis in ProPre and ProTreat than in control and cisplatin groups (Fig. 3D), suggesting that the intestinal inflammation could be attenuated in the Prohep groups due to the antiinflammatory characteristics of this species (26). Besides the significantly increased species, we also noticed that the major Th17-inducing bacteria, segmented filamentous bacteria (SFB), decreased dramatically in the ProPre and ProTreat groups but remained at a similar level in the control group, suggesting that the proinflammation activities from particular pathogens in the intestine were also suppressed upon probiotics feeding.…”

Section: Probiotics Mediate the Structural And Functional Compositionmentioning

confidence: 62%

“…The relative abundance of Alistipes, a major SCFAs producer in gut (25), decreased in the control group but increased in the ProPre and ProTreat groups by 32% and 29%, respectively. Among other enriched genera in the ProPre group, Oscillibacter and Parabacteroides are associated with T-cell differentiation by enhancing and maintaining the IL-10 producing Treg cells (26,27). One major species of the genus Parabacteroides, Parabacteroides distasonis, has the ability to reduce the intestinal inflammation by inducing the antiinflammatory cytokine IL-10 and suppressing the secretion of inflammatory cytokine IL-17, IL-6, and IFN-γ (26).…”

Section: Probiotics Mediate the Structural And Functional Compositionmentioning

confidence: 99%

“…Among other enriched genera in the ProPre group, Oscillibacter and Parabacteroides are associated with T-cell differentiation by enhancing and maintaining the IL-10 producing Treg cells (26,27). One major species of the genus Parabacteroides, Parabacteroides distasonis, has the ability to reduce the intestinal inflammation by inducing the antiinflammatory cytokine IL-10 and suppressing the secretion of inflammatory cytokine IL-17, IL-6, and IFN-γ (26). Oscillibacter is a valerate producer and capable of enhancing the differentiation of IL-10 producing Tregs in vivo (27).…”

Section: Probiotics Mediate the Structural And Functional Compositionmentioning

confidence: 99%

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Probiotics modulated gut microbiota suppresses hepatocellular carcinoma growth in mice

Sung

Lee

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

501

386

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The beneficial roles of probiotics in lowering the gastrointestinal inflammation and preventing colorectal cancer have been frequently demonstrated, but their immunomodulatory effects and mechanism in suppressing the growth of extraintestinal tumors remain unexplored. Here, we adopted a mouse model and metagenome sequencing to investigate the efficacy of probiotic feeding in controlling s.c. hepatocellular carcinoma (HCC) and the underlying mechanism suppressing the tumor progression. Our result demonstrated that Prohep, a novel probiotic mixture, slows down the tumor growth significantly and reduces the tumor size and weight by 40% compared with the control. From a mechanistic point of view the down-regulated IL-17 cytokine and its major producer Th17 cells, whose levels decreased drastically, played critical roles in tumor reduction upon probiotics feeding. Cell staining illustrated that the reduced Th17 cells in the tumor of the probiotictreated group is mainly caused by the reduced frequency of migratory Th17 cells from the intestine and peripheral blood. In addition, shotgun-metagenome sequencing revealed the crosstalk between gut microbial metabolites and the HCC development. Probiotics shifted the gut microbial community toward certain beneficial bacteria, including Prevotella and Oscillibacter, that are known producers of antiinflammatory metabolites, which subsequently reduced the Th17 polarization and promoted the differentiation of antiinflammatory Treg/Tr1 cells in the gut. Overall, our study offers novel insights into the mechanism by which probiotic treatment modulates the microbiota and influences the regulation of the T-cell differentiation in the gut, which in turn alters the level of the proinflammatory cytokines in the extraintestinal tumor microenvironment.H epatocellular carcinoma (HCC) is one of the most common cancers, the sixth most common neoplasm, and the second most deadly type of cancer worldwide (1). The traditional HCC treatment, including surgical treatment, local ablation therapy, and chemotherapy, could offer potential cure, yet patients are facing many limitations including the poor hepatic reserve. HCC is clearly a disease for which alternative therapeutic strategies must be developed. A better understanding of the interactions between cancer cells and stromal components in the tumorassociated proinflammatory microenvironment would be important for the management of this disease.The tumor microenvironment is infiltrated with various immune cells such as T cells, macrophages, neutrophils, natural killer (NK) cells, and myeloid-derived suppressor cells. Inflammation is known to play a pivotal role in tumor development by escalating tumor angiogenesis and cell growth. Once a solid tumor is formed, inflammation arises in the tumor-promoting direction. At the same time, new vasculature is needed in the tumor to provide nutrients and oxygen to support the growth of cancer cells, and this process plays a critical role in HCC, a highly vascularized tumor (2). Inflammation and angiogene...

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“…78 Furthermore, we found that this effect could be modulated via the manipulation of the gut microbiota and immunomodulation of the mucosal and the systemic immune response. 79 Thus, the mechanisms of this protective and therapeutic effect should be elucidated more precisely, and this novel approach may be used for the development of a potential vaccine.…”

Section: Inflammatory Bowel Disease (Ibd)mentioning

confidence: 99%