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Review highlights therapeutic potential of gut microbiome research
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While research on the gut microbiome and its relevance to health and disease is still in its early stages, the data so far suggest that therapies involving modification of the gut microbiota may show promise for several chronic diseases, according to a review article published in the New England Journal of Medicine.
“We were asked by the NEJM editor to highlight the most promising therapeutic and/or preventive perspectives of the more basic research done during the recent 5 years with exploitations of the human intestinal microbiome,” Oluf Pedersen, MD, DMSc, of the Novo Nordisk Foundation Center for Basic Metabolic Research, faculty of health and medical science at University of Copenhagen, told Healio Gastroenterology. “The progress and potential of human microbiota in cancer immunotherapy stands out as the most exciting and promising, especially the preclinical studies in rodents showing that human commensal bacteria given together with checkpoint blockade immunotherapy are able to enhance the effect of immunotherapy of several tumor types.”
Oluf Pedersen
In addition, Pedersen and his co-author Susan V. Lynch, PhD, of the division of gastroenterology, department of medicine at University of California, San Francisco, highlighted the high efficacy of fecal microbiota transplantation in recurrent Clostridium difficile infection as the “prime proof of principle that healthy gut microbiota can reproducibly correct a severe and specific microbial dysbiosis and that transplantation of healthy microbiota is therefore medically actionable.”
For chronic inflammatory bowel disease, however, success rates are more modest, but research efforts on the therapeutic potential of modifying the gut microbiota to treat IBD are ongoing.
“Within the field of gastroenterology and the therapeutic potential of gut microbiota we want to draw attention to recent studies demonstrating how a cocktail of 17 human clostridium strains has been shown to diminish the severity of experimental colitis in rodents through mechanisms that promote the expansion and activity of [regulatory T] cells,” Pedersen said. “This gives an inspiration to explore further bacterio-therapy based experiments in various form of chronic colitis in animals and humans.”
A wealth of preclinical research is underway across a range of chronic diseases, including cancer as well as inflammatory, metabolic, cardiovascular, autoimmune, neurologic and psychiatric conditions, which Pedersen and Lynch described in detail. They cautioned, however, the extrapolation of basic findings in rodent models to predictions of similar effects in humans, emphasizing that controlled clinical trials of probiotics, for example, have so far shown relatively modest therapeutic effects.
Despite the early age of this field of study, preliminary data suggest dietary interventions targeting gut microbiota appear to be major short- and long-term regulators of the structure and function of the gut microbiome, they wrote. While more clinical trials are needed, early findings, “in aggregate, support the view that specific dietary regimens, used along or combined with the administration of mixtures of microbial species that have been validated and approved by regulatory authorities (next-generation synbiotics), may hold potential for enhancing public health,” they concluded. – by Adam Leitenberger
Disclosures: Pederson reports no relevant financial disclosures. Lynch reports grant support from the Broad Foundation, the NIH/NIAID, the Sloan Foundation, Pfizer Inc., and Gilead Sciences; grant support and personal fees from Janssen; personal fees from Boston Consulting Group and Regeneron; and other support from Siolta Therapeutics outside the submitted work. In addition, Lynch reports several patents; please see the full study for details.
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