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Antibacterial Monoclonal Antibodies Do Not Disrupt the Intestinal Microbiome or Its Function

ABSTRACT: Antibiotics revolutionized medicine, however, it is now clear that broad-spectrum antibiotics alter the composition and function of the host’s microbiome. The microbiome plays a key role in human health and its perturbation is increasingly recognized as contributing to many human diseases. Wide spread broad-spectrum antibiotic use has also resulted in the emergence of multi-drug resistant pathogens, spurring development of pathogen-specific strategies such as monoclonal antibodies (mAbs) to combat bacterial infection. Not only are pathogen-specific approaches not expected to induce resistance in non-targeted bacteria, but they are hypothesized to have minimal impact on the gut microbiome. Here, we compare the effects of antibiotics, pathogen-specific mAbs or their controls (saline or c-IgG) on the gut microbiome of 7-week-old, female, C57BL/6 mice. The magnitude of change in taxonomic abundance, bacterial diversity, and bacterial metabolites including short chain fatty acids (SCFA) and bile acids in the fecal pellets from mice treated with pathogen-specific mAbs was no different from animals treated with saline or an IgG control. Conversely, dramatic changes were observed in the relative abundance, as well as alpha- and beta-diversity, of the fecal microbiome, and bacterial metabolites in the feces of all antibiotic-treated mice. Taken together, these results indicate that pathogen-specific mAbs do not alter the fecal microbiome like broad-spectrum antibiotics and may represent a safer, more targeted approach to antibacterial therapy.

INSTRUMENT(S): Liquid Chromatography MS - negative - reverse phase

SUBMITTER: Matthew Glover

PROVIDER: MTBLS1257 | MetaboLights | 2021-01-11

REPOSITORIES: MetaboLights

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Project description:Leber2015 - Mucosal immunity and gut microbiome interaction during C. difficile infection This model is described in the article: Systems Modeling of Interactions between Mucosal Immunity and the Gut Microbiome during Clostridium difficile Infection. Leber A, Viladomiu M, Hontecillas R, Abedi V, Philipson C, Hoops S, Howard B, Bassaganya-Riera J. PLoS ONE 2015; 10(7): e0134849 Abstract: Clostridium difficile infections are associated with the use of broad-spectrum antibiotics and result in an exuberant inflammatory response, leading to nosocomial diarrhea, colitis and even death. To better understand the dynamics of mucosal immunity during C. difficile infection from initiation through expansion to resolution, we built a computational model of the mucosal immune response to the bacterium. The model was calibrated using data from a mouse model of C. difficile infection. The model demonstrates a crucial role of T helper 17 (Th17) effector responses in the colonic lamina propria and luminal commensal bacteria populations in the clearance of C. difficile and colonic pathology, whereas regulatory T (Treg) cells responses are associated with the recovery phase. In addition, the production of anti-microbial peptides by inflamed epithelial cells and activated neutrophils in response to C. difficile infection inhibit the re-growth of beneficial commensal bacterial species. Computational simulations suggest that the removal of neutrophil and epithelial cell derived anti-microbial inhibitions, separately and together, on commensal bacterial regrowth promote recovery and minimize colonic inflammatory pathology. Simulation results predict a decrease in colonic inflammatory markers, such as neutrophilic influx and Th17 cells in the colonic lamina propria, and length of infection with accelerated commensal bacteria re-growth through altered anti-microbial inhibition. Computational modeling provides novel insights on the therapeutic value of repopulating the colonic microbiome and inducing regulatory mucosal immune responses during C. difficile infection. Thus, modeling mucosal immunity-gut microbiota interactions has the potential to guide the development of targeted fecal transplantation therapies in the context of precision medicine interventions. This model is hosted on BioModels Database and identified by: BIOMD0000000583. To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

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Antibacterial Monoclonal Antibodies Do Not Disrupt the Intestinal Microbiome or Its Function

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