Gut Microbiota and Intestinal Inflammation

Abstract Abstract SCI-49 Numerous studies of the microbiota that are found throughout the human body are under way, with the goal of unraveling the role of microbes in human physiology. Using experimental colitis models, we are investigating microbes that may instigate chronic inflammation, and we are studying putative beneficial microbes whose reduced presence may impact not only host response to the microbiota but also the behavior of the endogenous microbiota. Genomic approaches, combined with following microbial community response to a spectrum of dietary and pharmacologic perturbations, are shedding light on the dynamic operations of the microbiota that influence health and disease. Chronic inflammation in the intestine is not only the central pathophysiologic mechanism of inflammatory bowel disease (IBD) but also a key contributor to colorectal cancer. Ongoing work on the colorectal microbiome, using experimental models and human tumors, will be discussed. Collectively, our studies support the utility of wedding culture-independent and culture-dependent studies with mouse models for defining how the gut microbiota works in concert with the mucosal immune system to shape disease susceptibility for IBD and colorectal cancer. Disclosures: Garrett: Groupe Danone: Research Funding.

Download Full-text

A Crosstalk between Diet, Microbiome and microRNA in Epigenetic Regulation of Colorectal Cancer

Nutrients ◽

10.3390/nu13072428 ◽

2021 ◽

Vol 13 (7) ◽

pp. 2428

Author(s):

Małgorzata Guz ◽

Witold Jeleniewicz ◽

Anna Malm ◽

Izabela Korona-Glowniak

Keyword(s):

Colorectal Cancer ◽

Gastrointestinal Tract ◽

Gut Microbiota ◽

Intestinal Microbiota ◽

Current Knowledge ◽

Vital Role ◽

Disease States ◽

Health And Disease ◽

Dietary Components ◽

Non Coding Rnas

A still growing interest between human nutrition in relation to health and disease states can be observed. Dietary components shape the composition of microbiota colonizing our gastrointestinal tract which play a vital role in maintaining human health. There is a strong evidence that diet, gut microbiota and their metabolites significantly influence our epigenome, particularly through the modulation of microRNAs. These group of small non-coding RNAs maintain cellular homeostasis, however any changes leading to impaired expression of miRNAs contribute to the development of different pathologies, including neoplastic diseases. Imbalance of intestinal microbiota due to diet is primary associated with the development of colorectal cancer as well as other types of cancers. In the present work we summarize current knowledge with particular emphasis on diet-microbiota-miRNAs axis and its relation to the development of colorectal cancer.

Download Full-text

Dissecting the Interplay Mechanism between Epigenetics and Gut Microbiota: Health Maintenance and Disease Prevention

International Journal of Molecular Sciences ◽

10.3390/ijms22136933 ◽

2021 ◽

Vol 22 (13) ◽

pp. 6933

Author(s):

Yuqi Wu ◽

Chong-Zhi Wang ◽

Jin-Yi Wan ◽

Haiqiang Yao ◽

Chun-Su Yuan

Keyword(s):

Disease Prevention ◽

Gut Microbiota ◽

Intestinal Inflammation ◽

Epigenetic Factors ◽

Metabolic Disturbances ◽

Health Maintenance ◽

Full Life Cycle ◽

Research Profile ◽

Health And Disease ◽

New Perspective

The gut microbiota exists throughout the full life cycle of the human body, and it has been proven to have extensive impacts on health and disease. Accumulating evidence demonstrates that the interplay between gut microbiota and host epigenetics plays a multifaceted role in health maintenance and disease prevention. Intestinal microflora, along with their metabolites, could regulate multiple epigenetic pathways; e.g., DNA methylation, miRNA, or histone modification. Moreover, epigenetic factors can serve as mediators to coordinate gut microbiota within the host. Aiming to dissect this interplay mechanism, the present review summarizes the research profile of gut microbiota and epigenetics in detail, and further interprets the biofunctions of this interplay, especially the regulation of intestinal inflammation, the improvement of metabolic disturbances, and the inhibition of colitis events. This review provides new insights into the interplay of epigenetics and gut microbiota, and attempts to reveal the mysteries of health maintenance and disease prevention from this new perspective.

Download Full-text

Fecal Microbiota Transplantation Controls Murine Chronic Intestinal Inflammation by Modulating Immune Cell Functions and Gut Microbiota Composition

Cells ◽

10.3390/cells8060517 ◽

2019 ◽

Vol 8 (6) ◽

pp. 517 ◽

Cited By ~ 12

Author(s):

Claudia Burrello ◽

Maria Rita Giuffrè ◽

Angeli Dominique Macandog ◽

Angelica Diaz-Basabe ◽

Fulvia Milena Cribiù ◽

...

Keyword(s):

Ulcerative Colitis ◽

Gut Microbiota ◽

Immune Cells ◽

Intestinal Inflammation ◽

Fecal Microbiota Transplantation ◽

Experimental Colitis ◽

Fecal Microbiota ◽

Microbiota Composition ◽

Chronic Intestinal Inflammation ◽

Gut Microbiota Composition

Different gastrointestinal disorders, including inflammatory bowel diseases (IBD), have been linked to alterations of the gut microbiota composition, namely dysbiosis. Fecal microbiota transplantation (FMT) is considered an encouraging therapeutic approach for ulcerative colitis patients, mostly as a consequence of normobiosis restoration. We recently showed that therapeutic effects of FMT during acute experimental colitis are linked to functional modulation of the mucosal immune system and of the gut microbiota composition. Here we analysed the effects of therapeutic FMT administration during chronic experimental colitis, a condition more similar to that of IBD patients, on immune-mediated mucosal inflammatory pathways. Mucus and feces from normobiotic donors were orally administered to mice with established chronic Dextran Sodium Sulphate (DSS)-induced colitis. Immunophenotypes and functions of infiltrating colonic immune cells were evaluated by cytofluorimetric analysis. Compositional differences in the intestinal microbiome were analyzed by 16S rRNA sequencing. Therapeutic FMT in mice undergoing chronic intestinal inflammation was capable to decrease colonic inflammation by modulating the expression of pro-inflammatory genes, antimicrobial peptides, and mucins. Innate and adaptive mucosal immune cells manifested a reduced pro-inflammatory profile in FMT-treated mice. Finally, restoration of a normobiotic core ecology contributed to the resolution of inflammation. Thus, FMT is capable of controlling chronic intestinal experimental colitis by inducing a concerted activation of anti-inflammatory immune pathways, mechanistically supporting the positive results of FMT treatment reported in ulcerative colitis patients.

Download Full-text

Antibiotics as Major Disruptors of Gut Microbiota

Frontiers in Cellular and Infection Microbiology ◽

10.3389/fcimb.2020.572912 ◽

2020 ◽

Vol 10 ◽

Author(s):

Jaime Ramirez ◽

Francisco Guarner ◽

Luis Bustos Fernandez ◽

Aldo Maruy ◽

Vera Lucia Sdepanian ◽

...

Keyword(s):

Gut Microbiota ◽

Adaptive Immune System ◽

Antibiotic Use ◽

Negative Effects ◽

Antibiotic Resistant ◽

Childhood Exposure ◽

Clostridioides Difficile ◽

Culture Independent ◽

Health And Disease ◽

And Function

Advances in culture-independent research techniques have led to an increased understanding of the gut microbiota and the role it plays in health and disease. The intestine is populated by a complex microbial community that is organized around a network of metabolic interdependencies. It is now understood that the gut microbiota is vital for normal development and functioning of the human body, especially for the priming and maturation of the adaptive immune system. Antibiotic use can have several negative effects on the gut microbiota, including reduced species diversity, altered metabolic activity, and the selection of antibiotic-resistant organisms, which in turn can lead to antibiotic-associated diarrhea and recurrent Clostridioides difficile infections. There is also evidence that early childhood exposure to antibiotics can lead to several gastrointestinal, immunologic, and neurocognitive conditions. The increase in the use of antibiotics in recent years suggests that these problems are likely to become more acute or more prevalent in the future. Continued research into the structure and function of the gut microbiota is required to address this challenge.

Download Full-text

The Role of the Gut Microbiome in Colorectal Cancer

Clinics in Colon and Rectal Surgery ◽

10.1055/s-0037-1602239 ◽

2018 ◽

Vol 31 (03) ◽

pp. 192-198 ◽

Cited By ~ 14

Author(s):

Grace Chen

Keyword(s):

Colorectal Cancer ◽

Colon Cancer ◽

Microbial Community ◽

Gut Microbiota ◽

Gut Microbiome ◽

Intestinal Health ◽

Genotoxic Effects ◽

Bacterial Populations ◽

Health And Disease

AbstractThere is increasing evidence that the gut microbiome, which consists of trillions of microbes representing over 1,000 species of bacteria with over 3 million genes, significantly impacts intestinal health and disease. The gut microbiota not only is capable of promoting intestinal homeostasis and antitumor responses but can also contribute to chronic dysregulated inflammation as well as have genotoxic effects that lead to carcinogenesis. Whether the gut microbiota maintains health or promotes colon cancer may ultimately depend on the composition of the gut microbiome and the balance within the microbial community of protective and detrimental bacterial populations. Disturbances in the normal balanced state of a healthful microbiome, known as dysbiosis, have been observed in patients with colorectal cancer (CRC); however, whether these alterations precede and cause CRC remains to be determined. Nonetheless, studies in mice strongly suggest that the gut microbiota can modulate susceptibility to CRC, and therefore may serve as both biomarkers and therapeutic targets.

Download Full-text

Microbiota and Colorectal Cancer: From Gut to Bedside

Frontiers in Pharmacology ◽

10.3389/fphar.2021.760280 ◽

2021 ◽

Vol 12 ◽

Author(s):

Miguel Silva ◽

Valentina Brunner ◽

Markus Tschurtschenthaler

Keyword(s):

Colorectal Cancer ◽

Gut Microbiota ◽

Immune Cell ◽

Tumour Progression ◽

Cellular Transformation ◽

Intestinal Epithelial ◽

Therapeutic Drugs ◽

New Findings ◽

Current Therapies ◽

Health And Disease

Colorectal cancer (CRC) is a complex condition with heterogeneous aetiology, caused by a combination of various environmental, genetic, and epigenetic factors. The presence of a homeostatic gut microbiota is critical to maintaining host homeostasis and determines the delicate boundary between health and disease. The gut microbiota has been identified as a key environmental player in the pathogenesis of CRC. Perturbations of the gut microbiota structure (loss of equilibrium and homeostasis) are associated with several intestinal diseases including cancer. Such dysbiosis encompasses the loss of beneficial microorganisms, outgrowth of pathogens and pathobionts and a general loss of local microbiota diversity and richness. Notably, several mechanisms have recently been identified how bacteria induce cellular transformation and promote tumour progression. In particular, the formation of biofilms, the production of toxic metabolites or the secretion of genotoxins that lead to DNA damage in intestinal epithelial cells are newly discovered processes by which the microbiota can initiate tumour formation. The gut microbiota has also been implicated in the metabolism of therapeutic drugs (conventional chemotherapy) as well as in the modulation of radiotherapy responses and targeted immunotherapy. These new findings suggest that the efficacy of a given therapy depends on the composition of the host’s gut microbiota and may therefore vary from patient to patient. In this review we discuss the role of host-microbiota interactions in cancer with a focus on CRC pathogenesis. Additionally, we show how gut bacteria can be exploited in current therapies and how mechanisms directed by microbiota, such as immune cell boost, probiotics and oncolytic bacteria, can be applied in the development of novel therapies.

Download Full-text

The Association between Gut Microbiota and Intestinal Toll-like Receptors Genes Expression in Adenomatous and Colorectal Cancerous patients

10.21203/rs.2.23741/v1 ◽

2020 ◽

Author(s):

Sama Rezasoltani ◽

Maryam Sharafkhah ◽

Hamid Asadzadeh Aghdaei ◽

Meysam Olfatifar ◽

Ehsan Nazemalhosseini Mojarad ◽

...

Keyword(s):

Colorectal Cancer ◽

Gut Microbiota ◽

Intestinal Microbiota ◽

Intestinal Inflammation ◽

Inflammatory Responses ◽

Bacteroides Fragilis ◽

Normal Group ◽

Adenomatous Polyposis ◽

Toll Like Receptors ◽

Genes Expression

Abstract Background: Toll-like receptor (TLR) signaling has been implicated in colorectal cancer (CRC) development. Intestinal microbiota can affect the expression of TLRs, which may induce inflammatory responses and impair the gut homeostasis. Here, we aimed to evaluate certain intestinal microbiota related to TLRs expression in colonic tissues of adenomatous polyposis and CRC patients. Results: Fecal and colonic tissue samples were collected from normal controls (NC), adenomatous (AP) cases and (CRC) patients via colonoscopy for CRC screening during 2016 to 2018. Fecal samples were collected to analyze intestinal bacteria including Streptococcus bovis , Enterococcus faecalis , Bacteroides fragilis , enterotoxigenic Bacteroides fragilis (ETBF) , Fusobacterium nucleatum , Porphyromonas gingivalis, Porphyromonas spp . and Roseburia spp . by real-time PCR. Gene expression of TLR2, TLR4 and TLR5 was examined in colonic tissues by qRT-PCR. Different abundant of gut bacteria were achieved in NC, AP and CRC groups. The genes expression of TLR2, TLR4 and TLR5 were significantly different in AP and CRC cases vs. normal group (P value <0.05). There was a significant relationship between TLR2, TLR4, TLR5 genes expression and Roseburia spp., P. gingivalis and ETBF quantity in normal group. Also significant association between TLR2, TLR4 genes expression levels and the quantity of S.bovis , ETBF, Roseburia spp. and E. faecalis in AP and CRC cases were achieved. Conclusion : Intestinal expression of TLR2, TLR4 and TLR5 is dynamic and depends on gut microbiota. Hence, altered immune activation in response to dysbiotic microbiota may promote intestinal inflammation in a group of patients with AP and CRC. Keyword: Adenomatous polyposis; colorectal cancer; gut microbiota; Toll-like receptors; intestinal inflammation

Download Full-text

The intestinal microbiota in the rat model: major breakthroughs from new technologies

Animal Health Research Reviews ◽

10.1017/s1466252312000072 ◽

2012 ◽

Vol 13 (1) ◽

pp. 54-63 ◽

Cited By ~ 19

Author(s):

Julie Tomas ◽

Philippe Langella ◽

Claire Cherbuy

Keyword(s):

Gut Microbiota ◽

Intestinal Microbiota ◽

New Technologies ◽

Molecular Profiling ◽

Experimental Models ◽

Laboratory Animals ◽

Laboratory Rodents ◽

Culture Independent ◽

Recent Developments ◽

Micro Organisms

AbstractThe mammalian intestine harbors a large and diverse community of micro-organisms, known as the intestinal microbiota. Recent developments in molecular profiling methods, mainly based on microbial 16S ribosomal RNA gene sequencing, have provided unprecedented insights into the make-up and diversity of intestinal microbial communities. Using these culture-independent analyses, gut microbiota of several mammals including laboratory rodents, have been revisited. The laboratory rat is one of the major species bred and kept for scientific research. Although this animal is bred in confined environments and subjected to procedures for satisfying health requirements that hamper natural colonization, some major features of mammalian gut microbiota are conserved. However, the gut microbiota varies according to the breeding conditions of the rats and this could impact reproducibility of the experimental models. Determining the non-pathogenic microbial community might be relevant in standards of quality control of laboratory animals. Molecular profiling techniques could be applied to document this information.

Download Full-text