Identification of New Potential Biotherapeutics from Human Gut Microbiota-Derived Bacteria

Cuffaro, Bernardo; Assohoun, Aka L W; Boutillier, Denise; Peucelle, Véronique; Desramaut, Jérémy; Boudebbouze, Samira; Croyal, Mikaël; Waligora‐Dupriet, Anne‐Judith; Rhimi, Moez; Grangette, Corinne; Maguin, Emmanuelle

doi:10.3390/microorganisms9030565

Cited by 17 publications

(32 citation statements)

References 70 publications

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“…Interestingly, we observed that all tested C. minuta strains had a significant protective action on intestinal barrier integrity. This is consistent with other observations in similar screening assays 19 . As a consequence, it was not possible to use this assay to discriminate between strains.…”

Section: Discussionsupporting

confidence: 94%

Selection of a novel strain of Christensenella minuta as a future biotherapy for Crohn’s disease

Relizani¹,

Corf²,

Kropp

et al. 2022

Sci Rep

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Microbiome-based therapies for inflammatory bowel diseases offer a novel and promising therapeutic approach. The human commensal bacteria of the species Christensenella minuta (C. minuta) have been reported consistently missing in patients affected by Crohn’s disease (CD) and have been documented to induce anti-inflammatory effects in human epithelial cells, supporting their potential as a novel biotherapy. This work aimed at selecting the most promising strain of C. minuta for future development as a clinical candidate for CD therapy. Here, we describe a complete screening process combining in vitro and in vivo assays to conduct a rational selection of a live strain of C. minuta with strong immunomodulatory properties. Starting from a collection of 32 strains, a panel of in vitro screening assays was used to narrow it down to five preclinical candidates that were further screened in vivo in an acute TNBS-induced rat colitis model. The most promising candidate was validated in vivo in two mouse models of colitis. The validated clinical candidate strain, C. minuta DSM 33715, was then fully characterized. Hence, applying a rationally designed screening algorithm, a novel strain of C. minuta was successfully identified as the most promising clinical candidate for CD.

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Section: Discussionsupporting

confidence: 94%

Selection of a novel strain of Christensenella minuta as a future biotherapy for Crohn’s disease

Relizani¹,

Corf²,

Kropp

et al. 2022

Sci Rep

View full text Add to dashboard Cite

show abstract

“…Examining closely the strain carried by an individual is all the more important since several in vitro and in vivo studies showed that P. distasonis properties (such as anti-inflammatory, promotion of GLP-1 production or barrier protection) were highly strain-specific. [61,62] The relation between P. distasonis and GLP-1 production is consistent with three clinical trials showing that RD improves satiety in healthy adults. [22,24,25] Given the impact of RD on specific strains of P. distasonis, we foresee that this fiber could be used to extend our understanding of its growth, function, and interaction with the host.…”

Section: Discussionsupporting

confidence: 81%

Diet Supplementation with NUTRIOSE, a Resistant Dextrin, Increases the Abundance of Parabacteroides distasonis in the Human Gut

Thirion

Silva

Oñate

et al. 2022

Molecular Nutrition Food Res

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Scope: An imbalance of the gut microbiota ("dysbiosis") is associated with numerous chronic diseases, and its modulation is a promising novel therapeutic approach. Dietary supplementation with soluble fiber is one of several proposed modulation strategies. This study aims at confirming the impact of the resistant dextrin NUTRIOSE (RD), a soluble fiber with demonstrated beneficial health effects, on the gut microbiota of healthy individuals. Methods and results: Fifty healthy women are enrolled and supplemented daily with either RD (n = 24) or a control product (n = 26) during 6 weeks. Characterization of the fecal metagenome with shotgun sequencing reveals that RD intake dramatically increases the abundance of the commensal bacterium Parabacteroides distasonis. Furthermore, presence in metagenomes of accessory genes from P. distasonis, coding for susCD (a starch-binding membrane protein complex) is associated with a greater increase of the species. This suggests that response to RD might be strain-dependent. Conclusion: Supplementation with RD can be used to specifically increase P. distasonis in gut microbiota of healthy women. The magnitude of the response may be associated with fiber-metabolizing capabilities of strains carried by subjects. Further research will seek to confirm that P. distasonis directly modulates the clinical effects observed in other studies.

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“…When the gut microbiome is disturbed, metabolites also fluctuate significantly [3]. Disturbance of this complex system is associated with diseases such as inflammatory bowel diseases (IBDs), which present with chronic persistent inflammation of the digestive tract [4,5]. Moreover, not only gastrointestinal mucosa-related diseases but also insulin resistance, obesity, and non-alcoholic fatty liver disease (NASH) have revealed that gut dysbiosis is one of the causes of abnormal host metabolism due to a decrease in beneficial bacteria [6][7][8].…”

Section: Introductionmentioning

confidence: 99%

Clostridium butyricum MIYAIRI 588 Modifies Bacterial Composition under Antibiotic-Induced Dysbiosis for the Activation of Interactions via Lipid Metabolism between the Gut Microbiome and the Host

et al. 2021

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The gut microbiome is closely related to gut metabolic functions, and the gut microbiome and host metabolic functions affect each other. Clostridium butyricum MIYAIRI 588 (CBM 588) upregulates protectin D1 production in host colon tissue following G protein-coupled receptor (GPR) 120 activation to protect gut epithelial cells under antibiotic-induced dysbiosis. However, how CBM 588 enhances polyunsaturated fatty acid (PUFA) metabolites remains unclear. Therefore, we focused on the metabolic function alterations of the gut microbiome after CBM 588 and protectin D1 administration to reveal the interaction between the host and gut microbiome through lipid metabolism during antibiotic-induced dysbiosis. Consequently, CBM 588 modified gut microbiome and increased the butyric acid and oleic acid content. These lipid metabolic modifications induced GPR activation, which is a trigger of ERK 1/2 signaling and directed differentiation of downstream immune cells in the host colon tissue. Moreover, endogenous protectin D1 modified the gut microbiome, similar to CBM 588. This is the first study to report that CBM 588 influences the interrelationship between colon tissue and the gut microbiome through lipid metabolism. These findings provide insights into the mechanisms of prevention and recovery from inflammation and the improvement of host metabolism by CBM 588.

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Identification of New Potential Biotherapeutics from Human Gut Microbiota-Derived Bacteria

Cited by 17 publications

References 70 publications

Selection of a novel strain of Christensenella minuta as a future biotherapy for Crohn’s disease

Selection of a novel strain of Christensenella minuta as a future biotherapy for Crohn’s disease

Diet Supplementation with NUTRIOSE, a Resistant Dextrin, Increases the Abundance of Parabacteroides distasonis in the Human Gut

Clostridium butyricum MIYAIRI 588 Modifies Bacterial Composition under Antibiotic-Induced Dysbiosis for the Activation of Interactions via Lipid Metabolism between the Gut Microbiome and the Host

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