Role of gut microbiota in type 2 diabetes pathophysiology.

Colorectal cancer (CRC) accounts for about 10% of all new cancer cases globally. Located at close proximity to the colorectal epithelium, the gut microbiota comprises a large population of microorganisms that interact with host cells to regulate many physiological processes, such as energy harvest, metabolism and immune response. Sequencing studies have revealed microbial compositional and ecological changes in patients with CRC, whereas functional studies in animal models have pinpointed the roles of several bacteria in colorectal carcinogenesis, including Fusobacterium nucleatum and certain strains of Escherichia coli and Bacteroides fragilis. These findings give new opportunities to take advantage of our knowledge on the gut microbiota for clinical applications, such as gut microbiota analysis as screening, prognostic or predictive biomarkers, or modulating microorganisms to prevent cancer, augment therapies and reduce adverse effects of treatment. This Review aims to provide an overview and discussion of the gut microbiota in colorectal neoplasia, including relevant mechanisms in microbiota-related carcinogenesis, the potential of utilizing the microbiota as CRC biomarkers, and the prospect for modulating the microbiota for CRC prevention or treatment. These scientific findings will pave the way to clinically translate the use of gut microbiota for CRC in the near future.

Gut microbiota in colorectal cancer: mechanisms of action and clinical applications

Recently, relationship between gut microbiota composition and development of obesity has been pointed. However, the gut microbiota composition of individual with obesity is not known yet. Therefore, this systematic review aimed to evaluate differences in profile of gut microbiota between individuals with obesity and individuals with normal weight. A search performed on August 2019 in the databases Pubmed, Scopus, Web of Science, Cochrane library, Lilacs and gray literature using the terms: "microbiota", "microbiome", "obesity", "obesity morbid", and "humans". Studies assessing the gut microbiota composition in adults with obesity and lean were included. Quality assessment was performed by Newcastle-Ottawa Quality Assessment Scale. Of the 12,496 studies, 32 were eligible and included in this review. Individuals with obesity have a greater Firmicutes/Bacteroidetes ratio, Firmicutes, Fusobacteria, Proteobacteria, Mollicutes, Lactobacillus (reuteri), and less Verrucomicrobia (Akkermansia muciniphila), Faecalibacterium (prausnitzii), Bacteroidetes, Methanobrevibacter smithii, Lactobacillus plantarum and paracasei. In addition, some bacteria had positive correlation and others negative correlation with obesity. Individuals with obesity showed profile of gut microbiota different than individual lean. These results may help in advances of the diagnosis and treatment of obesity.

Profile of the gut microbiota of adults with obesity: a systematic review

Probiotics improve gut microbiota dysbiosis in obese mice fed a high-fat or high-sucrose diet.

The gut microbiota is a dense and diverse ecosystem that is involved in many physiological functions as well as in disease pathogenesis. It is dominated by bacteria, which have been extensively studied in the past 15 years; however, other microorganisms, such as fungi, phages, archaea and protists, are also present in the gut microbiota. Exploration of the fungal component, namely, the mycobiota, is at an early stage, and several specific technical challenges are associated with mycobiota analysis. The number of fungi in the lower gastrointestinal tract is far lower than that of bacteria, but fungal cells are much larger and much more complex than bacterial cells. In addition, a role of the mycobiota in disease, notably in IBD, is indicated by both descriptive data in humans and mechanistic data in mice. Interactions between bacteria and fungi within the gut, their functional roles and their interplay with the host and its immune system are fascinating areas that researchers are just beginning to investigate. In this Review, we discuss the newest data on the gut mycobiota and explore both the technical aspects of its study and its role in health and gastrointestinal diseases. The authors review the newest data on the gut fungal microbiota. They explore technical aspects of its analysis, how the mycobiome is influenced by immune and environmental factors, including fungi–bacteria interactions, and links between the mycobiota and gut diseases.

The gut mycobiota: insights into analysis, environmental interactions and role in gastrointestinal diseases

OBJECTIVE To investigate the gut microbiota in healthy volunteers (HVs), patients with overweight (OW), and patients with obesity (OB), including those with acanthosis nigricans (AN) or without AN (N-AN). METHODS Microbial 16S rRNA genes were examined by using pyrosequencing technology and analyzed by using bioinformatics methods. RESULTS Subjects in the OW and OB groups showed severe disturbances in glycemic control, lipid profile, and inflammatory markers (all P < 0.05); patients with AN had worse metabolic status (P < 0.001) and a lower diversity of microbiota (P < 0.05). The OB and HV groups showed totally different gut microbiota composition. In the OB group, beneficial microbiotas including Bifidobacterium (0.01% vs. 0.05%, false discovery rate [FDR] = 4.27*10-5 ), anti-inflammatory Faecalibacterium (6.70% vs. 13.82%, FDR = 0.010), and butyrate-producing Ruminococcaceae were significantly decreased, whereas Bacillus (0.58% vs. 0.04%, FDR = 0.013) and potential opportunistic pathogens such as Fusobacterium (1.44% vs. 0.11%, FDR < 0.01) and Escherichia-Shigella (6.01% vs. 0.76%, FDR = 0.041) had outgrown dramatically. Function prediction revealed a significant increase in lipopolysaccharide biosynthesis proteins and bacterial invasion of epithelial cell-associated genes and a significant decrease in glucose and essential amino acid-related genes. CONCLUSIONS Gut microbiotas and their functions were significantly changed in obesity. More prospective studies on association and causality between microbiota and obesity are imperative and might contribute to the prevention, diagnosis, and treatment of obesity.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/oby.22088

Dysbiosis Signatures of Gut Microbiota Along the Sequence from Healthy, Young Patients to Those with Overweight and Obesity.

The aim of this study was to explore the gut microbiota profiles of colorectal cancer (CRC) patients and to examine the relationship between gut microbiota and other key molecular factors involved in CRC tumorigenesis. In this study, a 16S rDNA sequencing platform was used to identify possible differences in the microbiota signature between CRC and adjacent normal mucosal tissue. Differences in the microbiota composition in different anatomical colorectal tumor sites and their potential association with KRAS mutation were also explored. In this study, the number of Firmicutes and Actinobacteria decreased, while the number of Fusobacteria increased in the gut of CRC patients. In addition, at the genus level, Fusobacterium was identified as the key contributor to CRC tumorigenesis. In addition, a different distribution of gut microbiota in ascending and descending colon cancer samples was observed. Lipopolysaccharide biosynthesis-associated microbial genes were enriched in tumor tissues. Our study suggests that specific mucosa-associated microbiota signature and function are significantly changed in the gut of CRC patients, which may provide insight into the progression of CRC. These findings could also be of value in the creation of new prevention and treatment strategies for this type of cancer.

Mucosa-associated microbiota signature in colorectal cancer.

Microbiota refers to a colony of microorganisms, and they are found in all multicellular organisms. This colony plays a major role in both the physiology and disease of the organism it inhabits. Much attention has been paid to host-microbiota interactions, but there has been little investigation on its role in carcinogenesis. In this study, we characterized a fecal mycobiota, also known as fungal signature, for the first time with 131 subjects, comprising polyp and colorectal cancer (CRC) patients, as well as a healthy control population. The data obtained were analyzed to assess the biodiversity and composition of the fungi. The impacts of anatomic position and tumor stage on the mycobiota were also evaluated. Correlations between fungi were investigated using the Spearman test. We observed fungal dysbiosis in colon polyps and CRC, including decreased diversity in polyp patients, an increased Ascomycota/Basidiomycota ratio, and an increased proportion of opportunistic fungi Trichosporon and Malassezia, which might favor the progression of CRC. Subsequent analysis with regard to tumor stage demonstrated a lower diversity and significant mycobiota alteration in early-stage tumors. Finally, the fungal correlation showed a close relationship within the community and concomitantly revealed a dramatically structured discrepancy in each clinical phenotype. In conclusion, our study has uncovered a distinct fungal dysbiosis and an alteration in the fungal network, which could play important roles in polyp and CRC pathogenesis.

Dysbiosis signature of mycobiota in colon polyp and colorectal cancer

The ketogenic diet (KD) is a high-fat, adequate-protein, and very-low-carbohydrate diet regimen that mimics the metabolism of the fasting state to induce the production of ketone bodies. The KD has long been established as a remarkably successful dietary approach for the treatment of intractable epilepsy and has increasingly garnered research attention rapidly in the past decade, subject to emerging evidence of the promising therapeutic potential of the KD for various diseases, besides epilepsy, from obesity to malignancies. In this review, we summarize the experimental and/or clinical evidence of the efficacy and safety of the KD in different diseases, and discuss the possible mechanisms of action based on recent advances in understanding the influence of the KD at the cellular and molecular levels. We emphasize that the KD may function through multiple mechanisms, which remain to be further elucidated. The challenges and future directions for the clinical implementation of the KD in the treatment of a spectrum of diseases have been discussed. We suggest that, with encouraging evidence of therapeutic effects and increasing insights into the mechanisms of action, randomized controlled trials should be conducted to elucidate a foundation for the clinical use of the KD. 

/pdf/ketogenic-diet-for-human-diseases-the-underlying-mechanisms-6vgztxph.pdf

Cheng Kong

Papers

Probiotics improve gut microbiota dysbiosis in obese mice fed a high-fat or high-sucrose diet.

Dysbiosis Signatures of Gut Microbiota Along the Sequence from Healthy, Young Patients to Those with Overweight and Obesity.

Mucosa-associated microbiota signature in colorectal cancer.

Dysbiosis signature of mycobiota in colon polyp and colorectal cancer

Ketogenic diet for human diseases: the underlying mechanisms and potential for clinical implementations