The path towards microbiome-based metabolite treatment.
Suez Jotham,Elinav Eran
The increasing evidence pointing towards the involvement of the gut microbiome in multiple diseases, as well as its plasticity, renders it a desirable potential therapeutic target. Nevertheless, classical therapies based on the consumption of live probiotic bacteria, or their enrichment by prebiotics, exhibit limited efficacy. Recently, a novel therapeutic approach has been suggested based on metabolites secreted, modulated or degraded by the microbiome. As many of the host-microorganism interactions pertaining to human health are mediated by metabolites, this approach may be able to provide therapeutic efficacy while overcoming caveats of current microbiome-targeting therapies, such as colonization resistance and inter-individual variation in microbial composition. In this Perspective, we will discuss the evidence that supports pursuing the metabolite-based therapeutic approach as well as issues critical for its implementation. In a broader context, we will discuss how recent advances in microbiome research may improve and refine current treatment modalities, and the potential of combining them with metabolite-based interventions as a means of achieving a person-specific, integrated and efficient therapy.
Influence of the Gut Microbiome, Diet, and Environment on Risk of Colorectal Cancer.
Song Mingyang,Chan Andrew T,Sun Jun
Researchers have discovered associations between elements of the intestinal microbiome (including specific microbes, signaling pathways, and microbiota-related metabolites) and risk of colorectal cancer (CRC). However, it is unclear whether changes in the intestinal microbiome contribute to the development of sporadic CRC or result from it. Changes in the intestinal microbiome can mediate or modify the effects of environmental factors on risk of CRC. Factors that affect risk of CRC also affect the intestinal microbiome, including overweight and obesity; physical activity; and dietary intake of fiber, whole grains, and red and processed meat. These factors alter microbiome structure and function, along with the metabolic and immune pathways that mediate CRC development. We review epidemiologic and laboratory evidence for the influence of the microbiome, diet, and environmental factors on CRC incidence and outcomes. Based on these data, features of the intestinal microbiome might be used for CRC screening and modified for chemoprevention and treatment. Integrated prospective studies are urgently needed to investigate these strategies.
Compositional and Temporal Changes in the Gut Microbiome of Pediatric Ulcerative Colitis Patients Are Linked to Disease Course.
Schirmer Melanie,Denson Lee,Vlamakis Hera,Franzosa Eric A,Thomas Sonia,Gotman Nathan M,Rufo Paul,Baker Susan S,Sauer Cary,Markowitz James,Pfefferkorn Marian,Oliva-Hemker Maria,Rosh Joel,Otley Anthony,Boyle Brendan,Mack David,Baldassano Robert,Keljo David,LeLeiko Neal,Heyman Melvin,Griffiths Anne,Patel Ashish S,Noe Joshua,Kugathasan Subra,Walters Thomas,Huttenhower Curtis,Hyams Jeffrey,Xavier Ramnik J
Cell host & microbe
Evaluating progression risk and determining optimal therapy for ulcerative colitis (UC) is challenging as many patients exhibit incomplete responses to treatment. As part of the PROTECT (Predicting Response to Standardized Colitis Therapy) Study, we evaluated the role of the gut microbiome in disease course for 405 pediatric, new-onset, treatment-naive UC patients. Patients were monitored for 1 year upon treatment initiation, and microbial taxonomic composition was analyzed from fecal samples and rectal biopsies. Depletion of core gut microbes and expansion of bacteria typical of the oral cavity were associated with baseline disease severity. Remission and refractory disease were linked to species-specific temporal changes that may be implicative of therapy efficacy, and a pronounced increase in microbiome variability was observed prior to colectomy. Finally, microbial associations with disease-associated serological markers suggest host-microbial interactions in UC. These insights will help improve existing treatments and develop therapeutic approaches guiding optimal medical care.
Genetic Factors and the Intestinal Microbiome Guide Development of Microbe-Based Therapies for Inflammatory Bowel Diseases.
Cohen Louis J,Cho Judy H,Gevers Dirk,Chu Hiutung
The intestinal microbiota is a dynamic community of bacteria, fungi, and viruses that mediates mucosal homeostasis and physiology. Imbalances in the microbiome and aberrant immune responses to gut bacteria can disrupt homeostasis and are associated with inflammatory bowel diseases (IBDs) in humans and colitis in mice. We review genetic variants associated with IBD and their effects on the intestinal microbiome, the immune response, and disease pathogenesis. The intestinal microbiome, which includes microbial antigens, adjuvants, and metabolic products, affects the development and function of the intestinal mucosa, influencing inflammatory responses in the gut. Therefore, strategies to manipulate the microbiome might be used in treatment of IBD. We review microbe-based therapies for IBD and the potential to engineer patients' intestinal microbiota. We discuss how studies of patients with IBD and mouse models have advanced our understanding of the interactions between genetic factors and the gut microbiome, and challenges to the development of microbe-based therapies for IBD.
The Influence of the Gut Microbiome on Cancer, Immunity, and Cancer Immunotherapy.
Gopalakrishnan Vancheswaran,Helmink Beth A,Spencer Christine N,Reuben Alexandre,Wargo Jennifer A
The microbiome is receiving significant attention given its influence on a host of human diseases including cancer. Its role in response to cancer treatment is becoming increasingly apparent, with evidence suggesting that modulating the gut microbiome may affect responses to numerous forms of cancer therapy. A working knowledge of the microbiome is vital as we move forward in this age of precision medicine, and an understanding of the microbiome's influence on immune responses and cancer is key. It is also important to understand factors influencing the gut microbiome and strategies to manipulate the microbiome to augment therapeutic responses.