Presentation Title

Probiotic and commensal gut microbial therapies in multiple sclerosis and its animal models: A systematic literature review

Presenter's Name(s)

Lorrie L. Blais, UVMFollow

Project Collaborators

Dr. Dimitry N. Krementsov, Theresa L. Montgomery

Abstract

The need for alternative treatments for multiple sclerosis (MS) has triggered copious amounts of research into microbial therapies focused on manipulating the microbiota-gut-brain axis. The continually accruing evidence and heterogeneity across studies makes the true efficacies of such therapies unclear, yet critical to assess for design of future studies. Accordingly, this systematic review is intended to consolidate, clarify, and critically evaluate the current evidence for probiotic and commensal gut bacteria treatments as therapy for MS and its animal models. Systematic literature searches were performed across four databases to identify and assess the risk of bias of relevant studies. Bradford Hill criteria were used to semi-quantitatively evaluate each specific treatment type for clinical and mechanistic evidence of therapeutic efficacy, as well as overall coherence and replication across studies. A total of 36 studies (6 human, 30 animal) were assessed in this review, which varied widely in study design and bacterial treatments. Human trials demonstrated scant evidence of clinical outcome improvement, albeit with considerable improvement in secondary parameters. Animal studies typically demonstrated clinical disease improvement, along with supporting immunologic and microbiologic findings. However, as evaluated by the Bradford Hill criteria, many therapies had limited evidence of replicable findings, control of confounding, cessation effects, dose-response relationship, standardization, and mechanistic evidence. Several microbial treatment approaches were identified as currently the most promising. Future studies should focus on addressing the unsatisfied Bradford Hill criteria, as discussed in this review, to edge closer towards clinical implementation of these therapies, and ultimately provide cheaper, safer, and more durable treatments for MS.

Primary Faculty Mentor Name

Dimitry N. Krementsov

Secondary Mentor NetID

Pdeming, Eamiel

Secondary Mentor Name

Paula B. Deming, Eyal Amiel

Graduate Student Mentors

Theresa L. Montgomery

Status

Graduate

Student College

College of Nursing and Health Sciences

Program/Major

Medical Laboratory Science

Primary Research Category

Health Sciences

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Probiotic and commensal gut microbial therapies in multiple sclerosis and its animal models: A systematic literature review

The need for alternative treatments for multiple sclerosis (MS) has triggered copious amounts of research into microbial therapies focused on manipulating the microbiota-gut-brain axis. The continually accruing evidence and heterogeneity across studies makes the true efficacies of such therapies unclear, yet critical to assess for design of future studies. Accordingly, this systematic review is intended to consolidate, clarify, and critically evaluate the current evidence for probiotic and commensal gut bacteria treatments as therapy for MS and its animal models. Systematic literature searches were performed across four databases to identify and assess the risk of bias of relevant studies. Bradford Hill criteria were used to semi-quantitatively evaluate each specific treatment type for clinical and mechanistic evidence of therapeutic efficacy, as well as overall coherence and replication across studies. A total of 36 studies (6 human, 30 animal) were assessed in this review, which varied widely in study design and bacterial treatments. Human trials demonstrated scant evidence of clinical outcome improvement, albeit with considerable improvement in secondary parameters. Animal studies typically demonstrated clinical disease improvement, along with supporting immunologic and microbiologic findings. However, as evaluated by the Bradford Hill criteria, many therapies had limited evidence of replicable findings, control of confounding, cessation effects, dose-response relationship, standardization, and mechanistic evidence. Several microbial treatment approaches were identified as currently the most promising. Future studies should focus on addressing the unsatisfied Bradford Hill criteria, as discussed in this review, to edge closer towards clinical implementation of these therapies, and ultimately provide cheaper, safer, and more durable treatments for MS.