Common Plant Fiber Gel Doubled Rate of Tumor Eradication

AHA Publisher — Fri, 02 Jul 2021 07:00:02 +0000

University of Michigan via Newswise – Many people don’t realize that the trillions of bacteria, viruses, and fungi residing within the gastrointestinal tract––collectively called the gut microbiome–– are connected to overall health, and specifically to cancer. Manipulating the gut microbiome to produce “beneficial” commensal microbes, which protect the host from pathogens and can boost immune responses, among other things, could potentially help patients respond better to cancer drugs called immune checkpoint inhibitors, a type of immunotherapy. To that end, researchers at the University of Michigan have developed a new dietary fiber formulation that improves the potency of immunotherapies against cancer by modulating the gut microbiome. In the future, cancer patients treated with immune checkpoint blockers may benefit from consuming this inulin gel dietary fiber, said James Moon, the John G. Searle Associate Professor of Pharmaceutical Sciences in the College of Pharmacy. The findings appear in the June 24 issue Nature Biomedical Engineering. Inulin, a dietary fiber found in chicory root, Jerusalem artichoke and other plants, is a prebiotic that helps produce colon-residing commensal bacteria. By formulating inulin into a more colon-targeted inulin gel formulation, the team was able to provide a rich source of nutrients to allow beneficial gut microbes to expand more in the gastrointestinal tract. The inulin gel improved immune checkpoint inhibitor therapy in rodents with colon carcinoma as well as melanoma. For instance, when inulin gel was combined with an immune checkpoint inhibitor in a colon carcinoma rodent model, the rate of tumor eradication doubled (100% improvement), compared with the immune checkpoint inhibitor therapy alone. “Consumption of the inulin gel expanded and increased the number of beneficial microbes in tumor-bearing mice,” said Kai Han, postdoctoral fellow and first author of the study. “These are beneficial commensal microbes that are found in cancer patients who respond well to immune checkpoint inhibitors. “The current approaches to restoring a healthy gut microbiome include oral ingestion of defined probiotics or fecal microbiota transplantation,” Han said. “However, it would be very challenging to develop these as pharmaceutical products due to scale-up manufacturing and quality control.” The human microbiome has recently emerged as the next frontier in drug development. Intense research interest in the microbiome is driven by evidence linking the potential health benefits of modulating gut microbiota to treating various diseases, including cancer, diabetes, obesity and neurodegenerative diseases. In particular, a series of recent studies showed that the gut microbiome plays a crucial role in cancer patients’ response rate to immune checkpoint inhibitors, Moon said. “We and others have shown that the gut microbiome has a crucial role in our immune responses,” Han said. “Close to 70% of lymph nodes in our bodies are located in the gastrointestinal tract and therefore, microbes residing in the gastrointestinal tract closely interact with our immune cells. Maintaining a healthy gut microbiome nurtures our immune system so that our immune cells can effectively fight against cancer.” The group chose inulin because it wanted something that could be readily translated to the clinic. Inulin is a dietary fiber that is widely consumed by the public and is present in many plants. It’s used as a sugar substitute and in candies and butter. By making inulin into inulin gel, researchers found that inulin gel coats the gastrointestinal tract much better, leaving more nutrients to the commensal microbes. The inulin gel also works with anti-PD-1 plus anti-CTLA-4 combo-therapy, (widely used immune checkpoint inhibitors) that treat many types of cancer, Han said. Roughly 10-30% of cancer patients respond to immune checkpoint inhibitors, depending on the types of cancer, and there is risk of serious immune-related complications and side-effects, Moon said. For instance, inflammation in the gastrointestinal tract and skin are common. Previous studies have shown that inulin consumption may alleviate gastrointestinal inflammation, such as colitis and IBD. “So, inulin gel may alleviate gastrointestinal inflammation induced by immune checkpoint inhibitors and we are testing this idea now,” Moon said. To read the original article click here.

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Oat and Rye Bran Fibres Alter Gut Microbiota, Reducing Weight Gain and Hepatic Inflammation

AHA Publisher — Wed, 08 Jul 2020 07:00:06 +0000

University of Eastern Finland via Newswise – In a newly published experimental study, the consumption of dietary fibre from oat and rye brans supported the growth of beneficial gut microbiota, which in turn ameliorated cholesterol metabolism, enhanced gut barrier function and reduced hepatic inflammation. In addition, diets enriched with oat or rye bran were shown to attenuate weight gain. The effects of oat and rye were partly different, but both were beneficial for health. The study was conducted within the research collaboration between the Institute of Public Health and Clinical Nutrition of the University of Eastern Finland, VTT Technical Research Centre of Finland and the School of Biological Sciences of The University of Hong Kong. The health benefits of oat, rye and other whole grain products have been widely studied, and their use has been associated with decreased inflammation and improved glucose, lipid and adipose tissue metabolism in human and animal experimental research. In addition, they have been linked to a decreased risk of obesity, metabolic syndrome, cardiovascular diseases and type 2 diabetes. Different dietary fibres are also known to have differing health effects. Until recently, the mechanisms underlying the health effects or oat and rye bran fibres have not been well understood. Dietary fibre is known to induce changes in gut microbiota function and to thus modulate gut environment in a beneficial manner.How this modulation is associated with metabolic pathways is, however, largely unclear. The aim of this experimental study was to investigate differences in metabolites produced by gut microbiota and their interactions with host metabolism in response to supplementation with oat and rye bran fibres. The study was an animal experiment during which mice were fed a high-fat Western diet for 17 weeks. Two groups were fed the same diet enriched with 10% of either oat or rye bran. Among the various gut microbial metabolites, this study focused on those especially relevant to the development of fatty liver disease, which is often associated with obesity. Thus, microbial metabolites were assessed by measuring cecal short chain fatty acids (SCFAs), ileal and fecal bile acids, and the expression of genes related to tryptophan metabolism. The findings suggest that both brans have the capacity to create a favourable environment in the gut by supporting the growth of beneficial microbes. The abundance of Lactobacillus genera was increased in the oat group, whereas Bifidobacterium genera was increased in the rye group. Via these microbiota changes, oats modified bile acid-related receptor function and rye modified bile acid production, which led to an improved cholesterol metabolism. Both bran fibres enhanced the production of SCFAs, leading to improved gut integrity, reduced liver inflammation, and diversion of tryptophan metabolism to a more beneficial pathway, that is, from serotonin synthesis to microbial indole production. In addition, both oat and rye supplementation were shown to attenuate weight gain associated with a high-fat diet. To read the original article click here.

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Common Plant Fiber Gel Doubled Rate of Tumor Eradication

Oat and Rye Bran Fibres Alter Gut Microbiota, Reducing Weight Gain and Hepatic Inflammation