scholarly journals A comprehensive analysis of the microbiota composition and gene expression in colorectal cancer

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Qian Zhang ◽  
Huan Zhao ◽  
Dedong Wu ◽  
Dayong Cao ◽  
Wang Ma

Abstract Background The dysregulation of gut microbiota is pivotal in colorectal carcinogenesis. Meanwhile, altered gut microbiome may affect the development of intestinal diseases through interaction with the host genes. However, the synergy between the altered gut microbiota composition and differential expression of specific genes in colorectal cancer (CRC) remains elusive. Thus, we integrated the data from 16S rRNA gene sequences and RNA sequences to investigate the potential relationship between genes and gut microbes in patients with CRC. Results Compared with normal samples, the presence of Proteobacteria and Fusobacteria increased considerably in CRC samples; conversely, the abundance of Firmicutes and Spirochaetes decreased markedly. In particular, the genera Fusobacterium, Catenibacterium, and Shewanella were only detected in tumor samples. Meanwhile, a closely interaction between Butyricimonas and Clostridium was observed in the microbiome network. Furthermore, a total of 246 (differentially expressed genes) DEGs were identified between tumor and normal tissues. Both DEGs and microbiota were involved in bile secretion and steroid hormone biosynthesis pathways. Finally, genes like cytochrome P450 family 3 subfamily A member 4 (CYP3A4) and ATP binding cassette subfamily G member 2 (ABCG2) enriched in these two pathways were connected with the prognosis of CRC, and CRC patients with low expression level of CYP3A4 and ABCG2 had longer survival time. Conclusion Identifying the complicated interaction between gut microbiota and the DEGs contributed to further understand the pathogenesis of CRC, and these findings might enable better diagnosis and treatment of CRC patients.

2019 ◽  
Author(s):  
Qian Zhang ◽  
Huan Zhao ◽  
Dedong Wu ◽  
Dayong Cao ◽  
Wang Ma

Abstract Subject: The dysbiosis of gut microbiota is pivotal in colorectal carcinogenesis. However, the synergy between an altered gut microbiota composition and differential gene expression of specific genes in colorectal cancer (CRC) remains elusive. Method: The gut microbiota dataset with number SRP158779, which contained 19 CRC samples and 19 normal samples, was downloaded from the National Center for Biotechnology Information (NCBI) Sequence Read Archive (SRA) database. The 16S rRNA gene sequences from this dataset were clustered into operational taxonomic units (OTUs); thereafter, the OTUs that were differentially enriched in CRC were identified and classified, followed by prediction of their functions. Additionally, RNA sequencing data from CRC samples was obtained from The Cancer Genome Atlas project (TCGA), and the differentially expressed genes (DEGs) and enriched pathways were identified. Finally, similar pathways that were significantly enriched in both differential OTUs and DEGs were screened. Key genes related to these pathways were executed the prognosis analysis. Results: The presence of Proteobacteria and Fusobacteria increased considerably in CRC samples; conversely, the abundance of Firmicute and Spirochaetes decreased markedly. In particular, the genera Fusobacterium , Catenibacterium , and Shewanella were detectable in tumor samples. Moreover, 246 DEGs were identified between tumor and normal tissues. Both DEGs and microbiota were involved in bile secretion and steroid hormone biosynthesis pathways. Finally, CYP3A4 and ABCG2 expression in CRC was related to the prognostic outcomes of CRC patients. Conclusion: Identifying the complicated interplay between gut microbiota and the DEGs could help in further understanding the pathogenesis of CRC, and these findings would enable better diagnosis and treatment of CRC patients. Keywords: colorectal cancer, gut microflora, gene expression, pathways enrichment, survival analysis


2021 ◽  
Vol 20 (1) ◽  
pp. 68-76
Author(s):  
M. A. Sukhina ◽  
I. A. Lyagina ◽  
A. L. Safin ◽  
S. A. Frolov ◽  
V. N. Kashnikov

The aim of the review is to show possible links between intestinal microbiota and colorectal carcinogenesis, to describe the procarcinogenic properties of microorganisms associated with the development or proliferation of colorectal cancer. The gut microbiota plays a leading role in metabolism, providing important metabolites to the macroorganism. In humans, there is a spatial variability in the qualitative and quantitative microbiota composition. The intestinal microbiota provides the colony resistance, protecting it from colonization by opportunistic and pathogenic microorganisms. There is more and more data on the role of the gut microbiota in the development of colorectal cancer. The profound study of the gut microbiome in various populations is required, which will allow to identify other microorganisms associated with the development or proliferation of colorectal cancer. It can be used as biomarkers for colorectal cancer screening and predicting the response to immunotherapy.


2020 ◽  
Vol 69 (6) ◽  
pp. 854-863
Author(s):  
Catherine O'Reilly ◽  
Órla O’Sullivan ◽  
Paul D. Cotter ◽  
Paula M. O’Connor ◽  
Fergus Shanahan ◽  
...  

Introduction. Management of steroid-refractory ulcerative colitis has predominantly involved treatment with systemic cyclosporine A (CyA) and infliximab. Aim. The purpose of this study was to assess the effect of using a colon-targeted delivery system CyA formulation on the composition and functionality of the gut microbiota. Methodology. Ex vivo faecal fermentations from six healthy control subjects were treated with coated minispheres (SmPill) with (+) or without (−) CyA and compared with a non-treated control in a model colon system. In addition, the in vivo effect of the SmPill+CyA formulation was investigated by analysing the gut microbiota in faecal samples collected before the administration of SmPill+CyA and after 7 consecutive days of administration from eight healthy subjects who participated in a pilot study. Results. Analysis of faecal samples by 16S rRNA gene sequencing indicated little variation in the diversity or relative abundance of the microbiota composition before or after treatment with SmPill minispheres with or without CyA ex vivo or with CyA in vivo. Short-chain fatty acid profiles were evaluated using gas chromatography, showing an increase in the concentration of n-butyrate (P=0.02) and acetate (P=0.32) in the faecal fermented samples incubated in the presence of SmPill minispheres with or without CyA. This indicated that increased acetate and butyrate production was attributed to a component of the coated minispheres rather than an effect of CyA on the microbiota. Butyrate and acetate levels also increased significantly (P=0.05 for both) in the faecal samples of healthy individuals following 7 days’ treatment with SmPill+CyA in the pilot study. Conclusion. SmPill minispheres with or without CyA at the clinically relevant doses tested here have negligible direct effects on the gut microbiota composition. Butyrate and acetate production increased, however, in the presence of the beads in an ex vivo model system as well as in vivo in healthy subjects. Importantly, this study also demonstrates the relevance and value of using ex vivo colon models to predict the in vivo impact of colon-targeted drugs directly on the gut microbiota.


2020 ◽  
Author(s):  
Katarina Butorac ◽  
Martina Banic ◽  
Jasna Novak ◽  
Andreja Leboš Pavunc ◽  
Ksenija Uroic ◽  
...  

Abstract Background: The influence of an S-layer-carrying strain Lactobacillus brevis SF9B and a plantaricin-producing strain Lactobacillus plantarum SF9C on the gut microbiota composition was evaluated in the rats. Considering the probiotic potential of Lb. brevis SF9B, this study aimed to examine the antibacterial activity of Lb. plantarum SF9C and potential for their in vivo colonisation, which could be the basis for the investigation of their synergistic functionality. Results: A plantaricin-encoding cluster was identified in Lb. plantarum SF9C, a strain which efficiently inhibited the growth of Listeria monocytogenes ATCC®19111™ and Staphylococcus aureus 3048. Contrary to the plantaricin-producing SF9C strain, the S-layer-carrying SF9B strain excluded Escherichia coli 3014 and Salmonella enterica serovar Typhimurium FP1 from adhesion to Caco-2 cells. Finally, DGGE analysis of the V2-V3 region of the 16S rRNA gene confirmed the transit of two selected lactobacilli through the gastrointestinal tract (GIT). Microbiome profiling via the Illumina MiSeq platform revealed the prevalence of Lactobacillus spp. in the gut microbiota of rats suggesting their colonisation potential in GIT.Conclusion: The combined application of Lb. plantarum SF9C and Lb. brevis SF9B could influence the intestinal microbiota composition, which is reflected through the increased abundance of Lactobacillus genus, but also through altered abundances of other bacterial genera, either in the model of healthy or aberrant microbiota of rats. The obtained results contributed to the functional aspects of SF9C and SF9B strains which could be incorporated in the probiotic-containing functional foods and therefore have a beneficial influence on the gut microbiota composition.


mBio ◽  
2015 ◽  
Vol 6 (5) ◽  
Author(s):  
Sandi Wong ◽  
W. Zac Stephens ◽  
Adam R. Burns ◽  
Keaton Stagaman ◽  
Lawrence A. David ◽  
...  

ABSTRACT Gut microbiota influence the development and physiology of their animal hosts, and these effects are determined in part by the composition of these microbial communities. Gut microbiota composition can be affected by introduction of microbes from the environment, changes in the gut habitat during development, and acute dietary alterations. However, little is known about the relationship between gut and environmental microbiotas or about how host development and dietary differences during development impact the assembly of gut microbiota. We sought to explore these relationships using zebrafish, an ideal model because they are constantly immersed in a defined environment and can be fed the same diet for their entire lives. We conducted a cross-sectional study in zebrafish raised on a high-fat, control, or low-fat diet and used bacterial 16S rRNA gene sequencing to survey microbial communities in the gut and external environment at different developmental ages. Gut and environmental microbiota compositions rapidly diverged following the initiation of feeding and became increasingly different as zebrafish grew under conditions of a constant diet. Different dietary fat levels were associated with distinct gut microbiota compositions at different ages. In addition to alterations in individual bacterial taxa, we identified putative assemblages of bacterial lineages that covaried in abundance as a function of age, diet, and location. These results reveal dynamic relationships between dietary fat levels and the microbial communities residing in the intestine and the surrounding environment during ontogenesis. IMPORTANCE The ability of gut microbiota to influence host health is determined in part by their composition. However, little is known about the relationship between gut and environmental microbiotas or about how ontogenetic differences in dietary fat impact gut microbiota composition. We addressed these gaps in knowledge using zebrafish, an ideal model organism because their environment can be thoroughly sampled and they can be fed the same diet for their entire lives. We found that microbial communities in the gut changed as zebrafish aged under conditions of a constant diet and became increasingly different from microbial communities in their surrounding environment. Further, we observed that the amount of fat in the diet had distinct age-specific effects on gut community assembly. These results reveal the complex relationships between microbial communities residing in the intestine and those in the surrounding environment and show that these relationships are shaped by dietary fat throughout the life of animal hosts.


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Jason R. Catanzaro ◽  
Juliet D. Strauss ◽  
Agata Bielecka ◽  
Anthony F. Porto ◽  
Francis M. Lobo ◽  
...  

Abstract Immunoglobulin A is the dominant antibody isotype found in mucosal secretions and enforces host-microbiota symbiosis in mice, yet selective IgA-deficiency (sIgAd) in humans is often described as asymptomatic. Here, we determined the effects of IgA deficiency on human gut microbiota composition and evaluated the possibility that mucosal secretion of IgM can compensate for a lack of secretory IgA. We used 16S rRNA gene sequencing and bacterial cell sorting to evaluate gut microbiota composition and taxa-specific antibody coating of the gut microbiota in 15 sIgAd subjects and matched controls. Despite the secretion of compensatory IgM into the gut lumen, sIgAd subjects displayed an altered gut microbiota composition as compared to healthy controls. These alterations were characterized by a trend towards decreased overall microbial diversity as well as significant shifts in the relative abundances of specific microbial taxa. While secretory IgA in healthy controls targeted a defined subset of the microbiota via high-level coating, compensatory IgM in sIgAd subjects showed less specificity than IgA and bound a broader subset of the microbiota. We conclude that IgA plays a critical and non-redundant role in controlling gut microbiota composition in humans and that secretory IgA has evolved to maintain a diverse and stable gut microbial community.


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Martin Iain Bahl ◽  
Anabelle Legarth Honoré ◽  
Sanne Tygesen Skønager ◽  
Oliver Legarth Honoré ◽  
Tove Clausen ◽  
...  

AbstractOn many mink farms, antibiotics are used extensively during the lactation period to reduce the prevalence and severity of pre-weaning diarrhoea (PWD) in mink kits (also referred to as greasy kit syndrome). Concerns have been raised, that routine treatment of PWD with antibiotics could affect the natural successional development of the gut microbiota, which may have long lasting consequences. Here we investigated the effects of early life antibiotic treatment administered for 1 week (postnatal days 13–20). Two routes of antibiotic administration were compared to a non-treated control group (CTR, n = 24). Routes of administration included indirect treatment, through the milk from dams receiving antibiotics by intramuscular administration (ABX_D, n = 24) and direct treatment by intramuscular administration to the kits (ABX_K, n = 24). A tendency for slightly increased weight at termination (Day 205) was observed in the ABX_K group. The gut microbiota composition was profiled by 16S rRNA gene sequencing at eight time points between Day 7 and Day 205. A clear successional development of the gut microbiota composition was observed and both treatment regimens caused detectable changes in the gut microbiota until at least eight days after treatment ceased. At termination, a significant positive correlation was identified between microbial diversity and animal weight.


2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Mei Wang ◽  
Brooke Smith ◽  
Brock Adams ◽  
Miller Tran ◽  
Ryan Dilger ◽  
...  

Abstract Objectives Enterotoxigenic Escherichia coli (ETEC) are an important cause of diarrhea in human infants and young farm animals. Osteopontin (OPN), a glycoprotein present in high concentration in human milk, has immunomodulatory functions, which could indirectly impact the microbiota. Furthermore, a previous study has shown fecal microbiota composition differs between wild-type and OPN knockout mice. Herein, the effects of OPN-enriched algae on the gut microbiota composition and volatile fatty acid (VFA) concentrations of ETEC-infected piglets were assessed. Methods Naturally-farrowed piglets were sow-reared for 21 days and then randomized to two weaning diets: WT (formula + 1% wild-type algae) or OPN (formula + 1% OPN-enriched algae). On postnatal day (PND) 31, all piglets were infected orally with a live culture of ETEC (1010 colony-forming unit/3 mL dose) daily for three consecutive days. On PND 41, ascending colon (AC) contents were collected. Gut microbiota was assessed by sequencing V3-V4 regions of 16S rRNA gene and VFAs were determined by gas chromatography. Alpha-diversity and VFAs were analyzed using PROC MIXED procedure of SAS. Beta-diversity was evaluated by permutational multivariate analysis of variance (PERMANOVA) and differential abundance analysis on the bacterial genera was performed using DESeq2 package of R. Results Shannon indices were lower in the AC contents of OPN piglets compared to WT piglets. The overall colonic microbiota of OPN piglets differed from that of WT piglets (PERMANOVA P = 0.015). At genus level, OPN-enriched algae increased the abundance of Streptococcus, decreased the abundances of Sutterella, Candidatus Soleaferrea, dga-11 gut group, Rikenellaceae RC9 gut group, Ruminococcaceae UCG-010, unculturedRuminococcaceae, Prevotella 2 and 7 compared to piglets consuming wild-type algae (P < 0. 05). OPN piglets also had higher (P < 0.05) concentrations of acetate, propionate, butyrate and valerate compared to WT. Conclusions In ETEC infected piglets, 1% OPN-enriched algae decreased alpha-diversity and modulated the microbiota composition and VFA profiles compared to 1% WT algae. Other studies have shown that OPN inhibits biofilm formation in vitro, but future research is needed to assess in vivo microbiome-modulation mechanisms. Funding Sources Triton Algae Innovations.


2020 ◽  
Vol 12 (1) ◽  
Author(s):  
Michael R. Goldberg ◽  
Hadar Mor ◽  
Dafna Magid Neriya ◽  
Faiga Magzal ◽  
Efrat Muller ◽  
...  

Abstract Background Multiple studies suggest a key role for gut microbiota in IgE-mediated food allergy (FA) development, but to date, none has studied it in the persistent state. Methods To characterize the gut microbiota composition and short-chain fatty acid (SCFAs) profiles associated with major food allergy groups, we recruited 233 patients with FA including milk (N = 66), sesame (N = 38), peanut (N = 71), and tree nuts (N = 58), and non-allergic controls (N = 58). DNA was isolated from fecal samples, and 16S rRNA gene sequences were analyzed. SCFAs in stool were analyzed from patients with a single allergy (N = 84) and controls (N = 31). Results The gut microbiota composition of allergic patients was significantly different compared to age-matched controls both in α-diversity and β-diversity. Distinct microbial signatures were noted for FA to different foods. Prevotella copri (P. copri) was the most overrepresented species in non-allergic controls. SCFAs levels were significantly higher in the non-allergic compared to the FA groups, whereas P. copri significantly correlated with all three SCFAs. We used these microbial differences to distinguish between FA patients and non-allergic healthy controls with an area under the curve of 0.90, and for the classification of FA patients according to their FA types using a supervised learning algorithm. Bacteroides and P. copri were identified as taxa potentially contributing to KEGG acetate-related pathways enriched in non-allergic compared to FA. In addition, overall pathway dissimilarities were found among different FAs. Conclusions Our results demonstrate a link between IgE-mediated FA and the composition and metabolic activity of the gut microbiota.


2018 ◽  
Vol 120 (9) ◽  
pp. 1014-1022 ◽  
Author(s):  
Daniel Lin ◽  
Brandilyn A. Peters ◽  
Charles Friedlander ◽  
Hal J. Freiman ◽  
James J. Goedert ◽  
...  

AbstractIncreasing evidence indicates that gut microbiota may influence colorectal cancer risk. Diet, particularly fibre intake, may modify gut microbiota composition, which may affect cancer risk. We investigated the relationship between dietary fibre intake and gut microbiota in adults. Using 16S rRNA gene sequencing, we assessed gut microbiota in faecal samples from 151 adults in two independent study populations: National Cancer Institute (NCI), n 75, and New York University (NYU), n 76. We calculated energy-adjusted fibre intake based on FFQ. For each study population with adjustment for age, sex, race, BMI and smoking, we evaluated the relationship between fibre intake and gut microbiota community composition and taxon abundance. Total fibre intake was significantly associated with overall microbial community composition in NYU (P=0·008) but not in NCI (P=0·81). In a meta-analysis of both study populations, higher fibre intake tended to be associated with genera of class Clostridia, including higher abundance of SMB53 (fold change (FC)=1·04, P=0·04), Lachnospira (FC=1·03, P=0·05) and Faecalibacterium (FC=1·03, P=0·06), and lower abundance of Actinomyces (FC=0·95, P=0·002), Odoribacter (FC=0·95, P=0·03) and Oscillospira (FC=0·96, P=0·06). A species-level meta-analysis showed that higher fibre intake was marginally associated with greater abundance of Faecalibacterium prausnitzii (FC=1·03, P=0·07) and lower abundance of Eubacterium dolichum (FC=0·96, P=0·04) and Bacteroides uniformis (FC=0·97, P=0·05). Thus, dietary fibre intake may impact gut microbiota composition, particularly class Clostridia, and may favour putatively beneficial bacteria such as F. prausnitzii. These findings warrant further understanding of diet–microbiota relationships for future development of colorectal cancer prevention strategies.


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