Association of Flavonifractor plautii, a Flavonoid-Degrading Bacterium, with the Gut Microbiome of Colorectal Cancer Patients in India

Abstract

Recently, dysbiosis in the human gut microbiome and shifts in the relative abundances of several bacterial species have been recognized as important factors in colorectal cancer (CRC). However, these studies have been carried out mainly in developed countries where CRC has a high incidence, and it is unclear whether the host-microbiome relationships deduced from these studies can be generalized to the global population. To test if the documented associations between the microbiome and CRC are conserved in a distinct context, we performed metagenomic and metabolomic association studies on fecal samples from 30 CRC patients and 30 healthy controls from two different locations in India, followed by a comparison of CRC data available from other populations. We confirmed the association of Bacteroides and other bacterial taxa with CRC that have been previously reported in other studies. However, the association of CRC with Flavonifractor plautii in Indian patients emerged as a novel finding. The plausible role of F. plautii appears to be linked with the degradation of beneficial anticarcinogenic flavonoids, which was also found to be significantly correlated with the enzymes and modules involved in flavonoid degradation within Indian CRC samples. Thus, we hypothesize that the degradation of beneficial flavonoids might be playing a role in cancer progression within this Indian cohort. We also identified 20 potential microbial taxonomic markers and 33 potential microbial gene markers that discriminate the Indian CRC from healthy microbiomes with high accuracy based on machine learning approaches. IMPORTANCE This study provides novel insights on the CRC-associated microbiome of a unique cohort in India, reveals the potential role of a new bacterium in CRC, and identifies cohort-specific biomarkers, which can potentially be used in noninvasive diagnosis of CRC. The study gains additional significance, as India is among the countries with a very low incidence of CRC, and the diet and lifestyle in India have been associated with a distinct gut microbiome in healthy Indians compared to other global populations. Thus, in this study, we hypothesize a unique relationship between CRC and the gut microbiome in an Indian population.

Changes in the fecal bacterial microbiota associated with disease severity in alcoholic hepatitis patients

“…13,15,22 The antibiotic-treated group in our study also had a significant increase in anaerobes Bilophila and Flavonifractor, both of which are rare clinical pathogens, but have been associated with systemic inflammation and/or colorectal malignancy. 23,26 However, whether antibiotic use is causatively linked to these observations, can not be answered with our study design.…”

Tumour Microbiome-Based Subtypes of Colorectal Cancer Correlate with Clinical Variables

“…So, while these genera are signi cantly depleted in mucosal samples compared to stool, a signi cant difference in abundance between location remained. Bi dobacterium was previously shown to have anti-cancerogenic effects [73,[90][91][92][93]. Similar association with left-sided and low-grade tumours showed 2 tumour genera (Lachnospira, Gemella) and Methanobrevibacter.…”

“…Amongst tumour genera of gut origin, Bacteroides, Escherichia-Shigella, Coprobacter, Coprococcus 1, Peptoclostridium (ex Clostridium di cile) [69], Howardella, Prevotella 1, Romboutsia, Eggerthella, Morganella, Enterococcus were previously associated with tumour mucosa [6,8,11,30,[69][70][71], while Lachnoclostridium, Flavonifractor [72,73], Sutterella and Hungatella (ex-Clostridium hathewayi) [74] were only reported increased in stool of patients with CRC.…”

Rice Bran and Quercetin Produce a Positive Synergistic Effect on Human Gut Microbiota, Elevate the Level of Propionate, and Reduce the Population of Enterobacteriaceae family when Determined using a Bioreactor Model

“…With a cut off Log2FC≥ 2 and p adj value > 0.05, Acidaminococcus intestine was the only enriched taxa in media supplemented with quercetin (QC) while Coprococcus catus, Dorea longicatena, Anaerostipes caccae, Eubacterium limosum and Enterococcus faecalis were highly reduced. Interestingly, the population of Flavonifractor plautii , a flavonoid metabolizing bacterium (46, 47) was significantly reduced in quercetin supplementation. The populations of F. plautii and Pseudoflavonifractor capillosus also were reduced in the group supplemented with quercetin and rice bran.…”