Microbiome and colorectal cancer: Roles in carcinogenesis and clinical potential

Molecular Aspects of Medicine, Journal Year: 2019, Volume and Issue: 69, P. 93 - 106

Published: May 24, 2019

The gastrointestinal tract harbors most of the microbiota associated with humans. In recent years, there has been a surge interest in assessing relationships between gut and several alterations, including colorectal cancer. Changes patients suffering cancer suggest possible role host-microbe interactions origin development this malignancy and, at same time, open door for novel ways preventing, diagnosing, or treating disease. review we survey current knowledge on healthy microbiome how it is altered other related disease conditions. describing past studies will critically assess technical limitations different approaches point to existing challenges research. We have special focus host-microbiome interaction mechanisms that may be important explain dysbiosis can lead chronic inflammation drive processes influence carcinogenesis tumor progression colon Finally, discuss potential developments microbiota-based therapeutics diagnostic tools

Language: Английский

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Systematic assessment of secondary bile acid metabolism in gut microbes reveals distinct metabolic capabilities in inflammatory bowel disease

Microbiome, Journal Year: 2019, Volume and Issue: 7(1)

Published: May 15, 2019

The human gut microbiome performs important functions in health and disease. A classic example for host-gut microbial co-metabolism is host biosynthesis of primary bile acids their subsequent deconjugation transformation by the microbiome. To understand these system-level host-microbe interactions, a mechanistic, multi-scale computational systems biology approach that integrates different types omic data needed. Here, we use systematic workflow to computationally model acid metabolism microbes communities.Therefore, first performed comparative genomic analysis biotransformation pathways 693 genomes expanded 232 curated genome-scale metabolic reconstructions with corresponding reactions (available at https://vmh.life ). We then predicted potential each microbe combination other microbes. found could produce maximally six 13 secondary silico, while pairs up 12 acids, suggesting being community task. investigate given microbiome, publicly available metagenomics from healthy Western individuals, as well inflammatory bowel disease patients controls, were mapped onto reconstructed strains. constructed individual large-scale personalized takes into account strain-level abundances. Using flux balance analysis, considerable variation deconjugate transform between microbiomes individuals. Moreover, pediatric significantly depleted production compared controls. contributions strain overall across individuals be distinct Finally, bottlenecks limiting identified model.This modeling provides novel way analyzing accelerate our understanding interactions diseases states. Our models tools are freely scientific community.

Language: Английский

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Lifestyle and dietary environmental factors in colorectal cancer susceptibility

Molecular Aspects of Medicine, Journal Year: 2019, Volume and Issue: 69, P. 2 - 9

Published: June 28, 2019

Language: Английский

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Impact of the gut microbiome on the genome and epigenome of colon epithelial cells: contributions to colorectal cancer development

Genome Medicine, Journal Year: 2019, Volume and Issue: 11(1)

Published: Feb. 25, 2019

In recent years, the number of studies investigating impact gut microbiome in colorectal cancer (CRC) has risen sharply. As a result, we now know that various microbes (and microbial communities) are found more frequently stool and mucosa individuals with CRC than healthy controls, including primary tumors themselves, even distant metastases. We also these induce mouse models, but little about how they colon epithelial cells (CECs) directly, or interactions might lead to modifications at genetic epigenetic levels trigger propagate tumor growth. Rates increasing younger individuals, remains second most frequent cause cancer-related deaths globally. Hence, in-depth understanding role play is needed. Here, review advances on genome epigenome CECs, as it relates CRC. Overall, numerous past few years have definitively shown exert distinct impacts DNA damage, methylation, chromatin structure non-coding RNA expression CECs. Some genes pathways altered by relate development, particularly those involved cell proliferation WNT signaling. need implement standardized analysis strategies, collate data from multiple studies, utilize models better assess effects, understand their functional relevance, leverage this information improve patient care.

Language: Английский

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Gut metabolomics profiling of non-small cell lung cancer (NSCLC) patients under immunotherapy treatment

Journal of Translational Medicine, Journal Year: 2020, Volume and Issue: 18(1)

Published: Feb. 3, 2020

Abstract Background Despite the efficacy of immune checkpoint inhibitors (ICIs) only 20–30% treated patients present long term benefits. The metabolic changes occurring in gut microbiota metabolome are herein proposed as a factor potentially influencing response to immunotherapy. Methods metabolomic profiling was characterized 11 affected by non-small cell lung cancer (NSCLC) with nivolumab second-line treatment anti-PD-1 nivolumab. metabolomics analyses were performed GC–MS/SPME and 1 H-NMR order detect volatile non-volatile metabolites. Metabolomic data processed statistical chemometric analyses. Results Four out (36%) presented early progression, while remaining 7 (64%) disease progression after 12 months. 2-Pentanone (ketone) tridecane (alkane) significantly associated on contrary short chain fatty acids (SCFAs) (i.e., propionate, butyrate), lysine nicotinic acid long-term beneficial effects. Conclusions Our preliminary suggest significant role pathways affecting approach could be promising strategy contribute personalized management identification microbiota-linked “indicators” progressor responder patients.

Language: Английский

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The association between fecal enterotoxigenic B. fragilis with colorectal cancer

BMC Cancer, Journal Year: 2019, Volume and Issue: 19(1)

Published: Sept. 5, 2019

Enterotoxigenic Bacteroides fragilis (ETBF) is an enterotoxin-producing bacterium that possibily has a role in the occurrence and progression of colorectal cancer (CRC) by modulating mucosal immune response inducing epithelial cell changes. The aim this study was to investigate frequency ETBF stool samples CRC patients healthy volunteers.A total 60 from confirmed volunteers with no personal or familial history diagnosis disease were collected. Stool screened for direct detection B. using PCR targeting marker genes neu bft. Enterotoxin isotypes bft-1, bft-2 bft-3 also detected positive samples.The among control cases 58.3 26.6%, respectively (P < 0.05). rate bft gene significantly higher than controls Also, presence stage III stages I II isotype 0.05).Our results show association between fecal CRC, we suggest may be potential diagnosis. However, additional investigations on tumor paired normal tissue are required substantiate possible correlation.

Language: Английский

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The contribution of gut bacterial metabolites in the human immune signaling pathway of non-communicable diseases

Gut Microbes, Journal Year: 2021, Volume and Issue: 13(1)

Published: Jan. 1, 2021

The interaction disorder between gut microbiota and its host has been documented in different non-communicable diseases (NCDs) such as metabolic syndrome, neurodegenerative disease, autoimmune disease. majority of these altered interactions arise through cross-talk immune system, inducing a low-grade chronic inflammation that characterizes all NCDs. In this review, we discuss the contribution bacterial metabolites to signaling pathways involved We then review recent advances aid rationally design microbial therapeutics. A deeper understanding intersections metabolism using metabolomics-based system biology platform promises reveal fundamental mechanisms drive predispositions disease suggest new avenues use therapeutic opportunities for NCDs treatment prevention.

Language: Английский

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Fecal Metabolomic Signatures in Colorectal Adenoma Patients Are Associated with Gut Microbiota and Early Events of Colorectal Cancer Pathogenesis

mBio, Journal Year: 2020, Volume and Issue: 11(1)

Published: Feb. 17, 2020

Colorectal adenomas are precursors of CRC. Recently, the gut microbiota, i.e., collection microbes residing in our gut, has been recognized as a key player CRC development. There have number microbiota profiling studies for colorectal adenoma and CRC; however, fewer considered metabolome, which serves chemical interface between host microbiota. Here, we conducted metabolome study analyzed metabolomic profiles together with paired composition profiles. We found several signatures that were associated some potentially indicative future This highlights potential early-driver metabolites pathogenesis guides further targeted experiments thus provides an important stepping stone toward developing better prevention strategies.

Language: Английский

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High fat diet, gut microbiome and gastrointestinal cancer

Theranostics, Journal Year: 2021, Volume and Issue: 11(12), P. 5889 - 5910

Published: Jan. 1, 2021

Gastrointestinal cancer is currently one of the main causes death, with a large number cases and wide range lesioned sites. A high fat diet, as public health problem, has been shown to be correlated various digestive system diseases tumors, can accelerate occurrence due inflammation altered metabolism. The gut microbiome focus research in recent years, associated cell damage or tumor immune microenvironment changes via direct extra-intestinal effects; this may facilitate development gastrointestinal tumors. Based on showing that both diet microbes promote imbalances intestinal microbes, we propose drives tumors by changing composition microbes.

Language: Английский

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Another renaissance for bile acid gastrointestinal microbiology

Nature Reviews Gastroenterology & Hepatology, Journal Year: 2024, Volume and Issue: 21(5), P. 348 - 364

Published: Feb. 21, 2024

Language: Английский

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