Decreased dietary fiber intake and structural alteration of gut microbiota in patients with advanced colorectal adenoma

Chen, Hui Min; Yu, You; Wang, Jilin; Yan, Lin; Kong, Xuan; Yang, Chang; Li, Yang; Liu, Zhanju; Yuan, Yao; Liu, Fei; Wu, Jian; Liu, Zhong; Fang, Dian Chun; Zou, Weiping; Fang, Jing

doi:10.3945/ajcn.112.046607

Cited by 269 publications

(219 citation statements)

References 42 publications

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“…In general there was an overall enrichment of the phylum Firmicutes, specifically the class Clostridia, in the Spanish cohort, which may reflect a higher content of fiber in their diet. Similar observations were previously reported in tumors compared to adjacent tissues, 67 and in feces of advanced adenomas 68 and CRC patients. 69 To investigate if, in addition to a tumor microenvironment compositional impact, there was an impact on bacterial function, we applied PICRUSt to the 16S rRNA amplicon sequencing data to infer bacterial metabolic functions.…”

Section: Discussionsupporting

confidence: 79%

Gut microbiome compositional and functional differences between tumor and non-tumor adjacent tissues from cohorts from the US and Spain

Delgado²,

et al. 2015

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Colorectal cancer (CRC) is the third most common cancer in the world and the second leading cause of cancer deaths in the US and Spain. The molecular mechanisms involved in the etiology of CRC are not yet elucidated due in part to the complexity of the human gut microbiota. In this study, we compared the microbiome composition of 90 tumor and matching adjacent tissue (adjacent) from cohorts from the US and Spain by 16S rRNA amplicon sequencing in order to determine the impact of the geographic origin on the CRC microbiome. Data showed a significantly (P < 0.05) higher Phylogenetic Diversity ( Predicted metagenome functional content from 16S rRNA surveys showed that bacterial motility proteins and proteins involved in flagellar assembly were over represented in adjacent tissues of both cohorts, while pathways involved in fatty acid biosynthesis, the MAPK signaling pathway, and bacterial toxins were over represented in tumors. Our study suggests that microbiome compositional and functional dissimilarities by geographic location should be taken in consideration when approaching CRC therapeutic options.

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Section: Discussionsupporting

confidence: 79%

Gut microbiome compositional and functional differences between tumor and non-tumor adjacent tissues from cohorts from the US and Spain

Delgado²,

et al. 2015

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“…Similar changes were also observed in patients with nosocomial diarrhea and Clostridium difficile-associated colitis [30]. A reduction in fecal butyrate has been found in patients with colorectal adenocarcinoma [31].…”

Section: Fig 1 Weight Of Rat Caecum In 1 Day (A) and 14 Days (B) Afsupporting

confidence: 62%

Fecal short-chain fatty acids at different time points after ceftriaxone administration in rats

Holota¹,

Holubenko²,

Остапчук³

et al. 2017

Ukr.Biochem.J.

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Short-chain fatty acids (SCFAs) T he interchange of low molecular weight metabolites between gut microorganisms and macroorganism have attracted a lot of attention during last years [1][2][3]. The gut microbiota affects predominantly host physiology by the production of short-chain fatty acids (SCFAs). SCFAs are saturated aliphatic organic acids that consist of one to six carbons of which acetate (C2), propionate (C3), and butyrate (C4) are most abundant (≥95%). Acetate, propionate, and butyrate are present in an approximate molar ratio of 60:20:20 in the colon and stool [4]. Depending on the diet, the total maximum concentration of SCFAs decreases from 70 to 140 mM in the proximal colon from 20 to 70 mM in the distal colon [5].These metabolites, especially butyrate, serve as an important source of energy for the intestinal epithelial cells, providing about 60-70% of their ener gy demand. Colonocytes from germ-free mice are in an energy-deprived state and exhibit decreased expression of enzymes that catalyze key steps in intermediary metabolism including the tricarboxylic acid cycle. Consequently, there is a marked decrease in NADH/NAD + , oxidative phosphorylation, and ATP levels, that results in AMP-activated protein kinase activation, cyclin-dependent kinase inhibitor 1B phosphorylation and autophagy. When butyrate is added to germ-free colonocytes, it rescues their deficit in mitochondrial respiration and prevents them from undergoing autophagy [6].

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“…1 Although the molecular mechanisms underlying these etiological factors are poorly characterized, complex interactions among dietary patterns, the host lifestyle and the intestinal microbiota contribute in affecting the biologic microenvironment in the large intestine. 1,22,23 Studies have reported that distinct tumor milieu in the proximal and distal segments of the large intestine associated with discrete mutation patterns. 24 In one study, colonic adenomas from various anatomic locations of the colon exhibited distinct DNA methylation clusters.…”

Section: Discussionmentioning

confidence: 99%

Aberrant expression of annexin A10 is closely related to gastric phenotype in serrated pathway to colorectal carcinoma

et al. 2015

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Annexin A10 (ANXA10) is a member of the ANX family that is normally expressed in gastric mucosa. ANXA10 was recently observed to be upregulated in sessile serrated adenoma, a precursor to microsatellite-unstable colorectal cancer. We investigated the use of ANXA10 in diagnosing colorectal carcinoma. In an immunohistochemical analysis, the intensity and quantity of ANXA10, MUC5AC, MUC6 and CDX2 in 123 colorectal carcinomas were graded. We determined the molecular status of BRAF and KRAS mutations, as well as the microsatellite instability status and the CpG island methylator phenotype in all colorectal carcinomas, and subcategorized into four molecular subgroups according to the molecular derangements. Nuclear ANXA10 staining was present in 36 colorectal carcinomas, exhibiting a strong significant association with the BRAF mutation status (Po0.0001) and positive CpG island methylator phenotype (Po0.0001), and a borderline significant association with high levels of microsatellite instability (P ¼ 0.072). The ANXA10-positive colorectal carcinomas were frequently positive for MUC5AC and MUC6, and were associated with absent or reduced CDX2 expression (all Po0.0001). According to a classification and regression tree analysis, ANXA10 is a superior marker for the molecular subtyping of colorectal carcinomas and represents a specific marker for colorectal cancers of the serrated pathway. Our results indicated that ANXA10 expression is implicated in gastric programming in serrated-pathway-associated colorectal carcinoma. ANXA10-positive colorectal carcinoma is highly associated with the molecular features of the serrated neoplasia pathway.

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Decreased dietary fiber intake and structural alteration of gut microbiota in patients with advanced colorectal adenoma

Abstract: A high-fiber dietary pattern and subsequent consistent production of SCFAs and healthy gut microbiota are associated with a reduced risk of A-CRA. This trial was registered at www.chictr.org as ChiCTR-TRC-00000123.

Cited by 269 publications

References 42 publications

Gut microbiome compositional and functional differences between tumor and non-tumor adjacent tissues from cohorts from the US and Spain

Gut microbiome compositional and functional differences between tumor and non-tumor adjacent tissues from cohorts from the US and Spain

Fecal short-chain fatty acids at different time points after ceftriaxone administration in rats

Aberrant expression of annexin A10 is closely related to gastric phenotype in serrated pathway to colorectal carcinoma

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