Normal Intestinal Microbiome Enhances Intestinal Barrier

MedicalResearch.com Interview with:



Dr. Venkatakrishna R Jala, PhD

Assistant Professor

James Graham Brown Cancer Center

Department of Microbiology and Immunology

University of Louisville

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Humans evolved along with their gut microbiota and adapted their physiological activities to help each other. Along with consumption of healthy diets, humans must harbor the appropriate microbiota to convert the foods into available components called metabolites. These microbial metabolites play a critical role in preserving homeostasis, the development of immune systems and preventing adverse events both systemically and locally. Despite the availability of large metagenomics (bacterial sequence) data, and its associations with disease conditions, the functional dynamics of microbiota (good vs bad) in human health or diseases are yet to be defined. The host’s indigenous gut microbiota and its metabolites have emerged as key factors that greatly influence human health and disease, including inflammatory bowel diseases (IBD). IBD patients suffer from leaky gut and increased inflammation.

The current study demonstrates that a microbial metabolite derived from ellagitannin/ellagic acid rich diets (e.g., pomegranate, berries) called ‘urolithin A’ and its synthetic analogue significantly enhance gut barrier function in addition to blocking the unwarranted inflammation in IBD animal models.

MedicalResearch.com: What should readers take away from your report?

Response: Some of the microbes in our gut have evolved to generate beneficial microbial metabolites from dietary products in the vicinity of the gut barrier. To keep this benefit, we need to consume a healthy diets well as harbor the appropriate bacteria that can metabolize those foods into active beneficial compounds. This study shows that direct consumption of one such microbial metabolite, UroA or its analog can compensate for a lack of the specific bacteria responsible for production of UroA and continuous consumption of the necessary foods, pomegranates and berries in treating colitis in animal models. Existing IBD treatments include utilizing anti-TNF-α antibodies to reduce inflammation. Here we suggest that treatment with UroA enhances gut barrier function (i.e., prevents leaky guts) in addition to blocking inflammation and might provide better therapeutic options for control of IBDs.

MedicalResearch.com: What recommendations do you have for future research as a result of this work?

Response: It is possible that excessive use of antibiotics and modern dietary trends led to microbial dysbiosis resulting in the elimination of some bacterial populations that are capable of producing beneficial metabolites. More rigorous and systematic studies are required to assess the benefits of direct consumption of metabolites in humans both in healthy and disease conditions, and whether supplementation of metabolites could overcome the dysbiosis. Overall, UroA/UAS03 will not only be effective in IBD-related diseases but may also prove to be therapeutic in other disorders involving barrier dysfunction and inflammation, such as alcohol liver diseases, neurological disorders, and colon cancers. This will require further studies.

While encouraging natural levels of UroA in the gut by consuming the appropriate foods and protecting populations of beneficial bacteria should have positive health effects, the researchers believe the use of the more stable synthetic UAS03 may prove to be therapeutically effective in cases of acute colitis. Further experiments and clinical testing are needed to test these beliefs.

MedicalResearch.com: Is there anything else you would like to add?

Response: It is possible that excessive use of antibiotics and modern dietary trends led to microbial dysbiosis resulting in the elimination of some bacterial populations that are capable of producing beneficial metabolites. More rigorous and systematic studies are required to assess the benefits of direct consumption of metabolites in humans both in healthy and disease conditions, and whether supplementation of metabolites could overcome the dysbiosis. Overall, UroA/UAS03 will not only be effective in IBD-related diseases but may also prove to be therapeutic in other disorders involving barrier dysfunction and inflammation, such as alcohol liver diseases, neurological disorders, and colon cancers. This will require further studies.

While encouraging natural levels of UroA in the gut by consuming the appropriate foods and protecting populations of beneficial bacteria should have positive health effects, the researchers believe the use of the more stable synthetic UAS03 may prove to be therapeutically effective in cases of acute colitis. Further experiments and clinical testing are needed to test these beliefs.

Response: Is there anything else you would like to add? Any disclosures?

Current study is a collaborative project between Venkatakrishna R JALA (University of Louisville, Louisville, KY, USA) and Praveen Kumar Vemula (inStem, Bangalore, INDIA).

Funding for the research includes NIH/NCI (R21CA216090), NIH/NIGMS (P20GM125504-01) and grants from U of L, Rounsavall Foundation, The Jewish Heritage Fund for Excellence

Research Enhancement Grant and the James Graham Brown Cancer Center. Additional support was obtained from NIH/NCI (CA191683), (P20GM103436), (P30GM106396) to Venkatakrishna Rao JALA, PhD.

Department of Biotechnology (DBT) (BT/PR12490/AAQ/3/716/2015) and the Institute for Stem Cell Biology and Regenerative Medicine (inStem), India to Praveen Kumar Vemula.

Several authors hold a patent application related to this technology.

Citation: Singh R, Chandrashekharappa S, Bodduluri SR, Baby BV, Hegde B, Kotla NG, Hiwale AA, Saiyed T, Patel P, Vijay-Kumar M, Langille MGI, Douglas GM, Cheng X, Rouchka EC, Waigel SJ, Dryden GW, Alatassi H, Zhang H-G, Haribabu B, Vemula PK, Jala VR. Enhancement of the gut barrier integrity by a microbial metabolite through the Nrf2 pathway. Nature Communications. 2019;10(1):89. doi: 10.1038/s41467-018-07859-7. Link: https://rdcu.be/bfS5x

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