Dietary Rice Bran-Modified Human Gut Microbial Consortia Confers Protection against Colon Carcinogenesis Following Fecal Transfaunation.

Kristopher D Parker,Rama Kant,Hend Ibrahim,Sangeeta Rao,Akhilendra K Maurya,Dileep Kumar,Petronella R Hove,Kristine A Kuhn,Komal Raina,Bupinder Raina,Elizabeth P Ryan,Rajesh Agarwal

doi:10.3390/biomedicines9020144

Abstract

Rice bran, removed from whole grain rice for white rice milling, has demonstrated efficacy for the control and suppression of colitis and colon cancer in multiple animal models. Dietary rice bran intake was shown to modify human stool metabolites as a result of modifications to metabolism by gut microbiota. In this study, human stool microbiota from colorectal cancer (CRC) survivors that consumed rice bran daily was examined by fecal microbiota transplantation (FMT) for protection from azoxymethane and dextran sodium sulfate (AOM/DSS) induced colon carcinogenesis in germ-free mice. Mice transfaunated with rice bran-modified microbiota communities (RMC) harbored fewer neoplastic lesions in the colon and displayed distinct enrichment of Flavonifractor and Oscillibacter associated with colon health, and the depletion of Parabacteroides distasonis correlated with increased tumor burden. Two anti-cancer metabolites, myristoylcarnitine and palmitoylcarnitine were increased in the colon of RMC transplanted mice. Trimethylamine-N-oxide (TMAO) and tartarate that are implicated in CRC development were reduced in murine colon tissue after FMT with rice bran-modified human microbiota. Findings from this study show that rice bran modified gut microbiota from humans confers protection from colon carcinogenesis in mice and suggests integrated dietary-FMT intervention strategies should be tested for colorectal cancer control, treatment, and prevention.

Highlights

The incidence of colorectal cancer is on the rise, today it is the world’s third most deadly cancer with almost 900,000 deaths annually [1] and is expected to increase by 60%to more than 2.2 million new cases and 1.1 million cancer deaths by 2030 [2]
Bacteroides fragilis, Enterococcus, and Parabacteroides distasonis were enriched in the control microbiota consortium (CMC-m) inoculums that had more colon tumors in mice and were absent from the RMCm inoculums that were protective against colon tumor formation
The depletion of Parabacteroides distasonis in mice transfaunated with Rice Bran Modified Microbial Consortia (RMC), which harbored fewer colonic lesions, is in contrast to a number of studies that have reported associations of P. distasonis with high tumor burdens [50], or pro-inflammatory activity increasing the severity of DSS-induced colitis [51]

Summary

Introduction

The incidence of colorectal cancer is on the rise, today it is the world’s third most deadly cancer with almost 900,000 deaths annually [1] and is expected to increase by 60%to more than 2.2 million new cases and 1.1 million cancer deaths by 2030 [2]. Colorectal cancer is a complex, malignant disease whose multi-stage development involves numerous genetic and environmental risk factors [3]. These risk factors include genetic abnormalities, 4.0/). Biomedicines 2021, 9, 144 age, alterations of the gut microbiota [3], and lifestyle-related factors such as smoking, alcohol use, and dietary factors including consumption of highly processed foods, animal fat, and red meat coupled with a low intake of fiber and fruits [4,5]. Microbial communities involved in the progression and advancement of colorectal cancer have been reviewed globally [3,7], with various studies showing microbiota connections to the development of gastrointestinal cancers [8,9]. In germ-free mice, lower incidence of chemically induced duodenal and colonic tumors were observed compared to those raised in conventional husbandry [10]

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