Accumulating evidence suggests that the human intestinal microbiota contributes to the aetiology of colorectal cancer (CRC), not only via the pro-carcinogenic activities of specific pathogens but ...also via the influence of the wider microbial community, particularly its metabolome. Recent data have shown that the short-chain fatty acids acetate, propionate and butyrate function in the suppression of inflammation and cancer, whereas other microbial metabolites, such as secondary bile acids, promote carcinogenesis. In this Review, we discuss the relationship between diet, microbial metabolism and CRC and argue that the cumulative effects of microbial metabolites should be considered in order to better predict and prevent cancer progression.
Our understanding of the microbial involvement in inflammatory bowel disease(IBD) pathogenesis has increased exponentially over the past decade. The development of newer molecular tools for the ...global assessment of the gut microbiome and the identification of nucleotide-binding oligomerization domain-containing protein 2 in 2001 and other susceptibility genes for Crohn’s disease in particular has led to better understanding of the aetiopathogenesis of IBD. The microbial studies have elaborated the normal composition of the gut microbiome and its perturbations in the setting of IBD. This altered microbiome or "dysbiosis" is a key player in the protracted course of inflammation in IBD. Numerous genome-wide association studies have identified further genes involved in gastrointestinal innate immunity(including polymorphisms in genes involved in autophagy: ATG16L1 and IGRM), which have helped elucidate the relationship of the local innate immunity with the adjacent luminal bacteria. These developments have also spurred the search for specific pathogens which may have a role in the metamorphosis of the gut microbiome from a symbiotic entity to a putative pathogenic one. Here we review advances in our understanding of microbial involvement in IBD pathogenesis over the past 10 years and offer insight into how this will shape our therapeutic management of the disease in the coming years.
The human gut microbiota plays a major role in the development and maintenance of good health. Many recent studies have attempted to define links between microbiota residents, their function and the ...development of colorectal cancer (CRC). Gut microbiota drive the development of inflammation within the colon and such inflammation is implicated in colonic neoplastic development. Although the precise mechanisms through which the microbiota is involved in cancer development remain elusive, the message is clear: the microbiota contributes to cancer risk by influencing a number of key host processes. It is also recognized that we have the ability to influence the role of the gut microbiota by considering our nutritional intake. We have always known that 'we are what we eat' but it is also true that 'they (our gut microbiota) are what we eat'. We therefore have a huge opportunity to positively influence our health through microbial manipulation. There is now a clear need to move past defining the constituents of the gastrointestinal microbiota and to focus more on understanding the functional capabilities of the resident microbial community and how this impacts on host health. One such emerging concept is the development of microbial biofilms which can form in the gut in conjunction with CRC tissue. By better understanding of the interaction between the host and its resident microbiota, in the context of health and cancer development, we will open new therapeutic and diagnostic opportunities for reducing the CRC global health burden.
Differences in microbiota composition in children with autism spectrum disorder (ASD) compared to unaffected siblings and healthy controls have been reported in various studies. This study aims to ...systematically review the existing literature concerning the role of the gut microbiota in ASD.
An extensive literature search was conducted using MEDLINE and EMBASE databases to identify studies (January 1966 through July 2019).
A total of 28 papers were included. The studies ranged from 12 to 104 participants who were aged between 2 and 18 years from various geographical areas. Majority of studies included faecal samples; however, 4 studies examined mucosal biopsies from different sites. The heterogeneity in ASD diagnostic methodology, gut site sampled and laboratory methods used made meta-analysis inappropriate. Species reported to be significantly higher in abundance in autistic children included Clostridium, Sutterella, Desulfovibrio and Lactobacillus. The findings are however inconsistent across studies. In addition, -potential confounding effects of antimicrobial use, gastrointestinal symptoms and diet on the gut microbiota are unclear due to generally poor assessment of these factors.
It is clear that the gut microbiota is altered in ASD, although further exploration is needed on whether this is a cause or an effect of the condition.
Increasing evidence links the gut microbiota with colorectal cancer. Metagenomic analyses indicate that symbiotic Fusobacterium spp. are associated with human colorectal carcinoma, but whether this ...is an indirect or causal link remains unclear. We find that Fusobacterium spp. are enriched in human colonic adenomas relative to surrounding tissues and in stool samples from colorectal adenoma and carcinoma patients compared to healthy subjects. Additionally, in the ApcMin/+ mouse model of intestinal tumorigenesis, Fusobacterium nucleatum increases tumor multiplicity and selectively recruits tumor-infiltrating myeloid cells, which can promote tumor progression. Tumors from ApcMin/+ mice exposed to F. nucleatum exhibit a proinflammatory expression signature that is shared with human fusobacteria-positive colorectal carcinomas. However, unlike other bacteria linked to colorectal carcinoma, F. nucleatum does not exacerbate colitis, enteritis, or inflammation-associated intestinal carcinogenesis. Collectively, these data suggest that, through recruitment of tumor-infiltrating immune cells, fusobacteria generate a proinflammatory microenvironment that is conducive for colorectal neoplasia progression.
•Fusobacterium is enriched in human adenomas, suggesting an early role in tumorigenesis•Fusobacterium nucleatum accelerates tumorigenesis in ApcMin/+ mice•F. nucleatum drives myeloid cell infiltration in intestinal tumors•Fusobacterium is associated with a proinflammatory signature in mouse and human tumors
Determining bacterial community structure in fecal samples through DNA sequencing is an important facet of intestinal health research. The impact of different commercially available DNA extraction ...kits upon bacterial community structures has received relatively little attention. The aim of this study was to analyze bacterial communities in volunteer and inflammatory bowel disease (IBD) patient fecal samples extracted using widely used DNA extraction kits in established gastrointestinal research laboratories.
Fecal samples from two healthy volunteers (H3 and H4) and two relapsing IBD patients (I1 and I2) were investigated. DNA extraction was undertaken using MoBio Powersoil and MP Biomedicals FastDNA SPIN Kit for Soil DNA extraction kits. PCR amplification for pyrosequencing of bacterial 16S rRNA genes was performed in both laboratories on all samples. Hierarchical clustering of sequencing data was done using the Yue and Clayton similarity coefficient.
DNA extracted using the FastDNA kit and the MoBio kit gave median DNA concentrations of 475 (interquartile range 228-561) and 22 (IQR 9-36) ng/µL respectively (p<0.0001). Hierarchical clustering of sequence data by Yue and Clayton coefficient revealed four clusters. Samples from individuals H3 and I2 clustered by patient; however, samples from patient I1 extracted with the MoBio kit clustered with samples from patient H4 rather than the other I1 samples. Linear modelling on relative abundance of common bacterial families revealed significant differences between kits; samples extracted with MoBio Powersoil showed significantly increased Bacteroidaceae, Ruminococcaceae and Porphyromonadaceae, and lower Enterobacteriaceae, Lachnospiraceae, Clostridiaceae, and Erysipelotrichaceae (p<0.05).
This study demonstrates significant differences in DNA yield and bacterial DNA composition when comparing DNA extracted from the same fecal sample with different extraction kits. This highlights the importance of ensuring that samples in a study are prepared with the same method, and the need for caution when cross-comparing studies that use different methods.
Treatment is a challenge in Irritable Bowel Syndrome (IBS) and fecal microbiota transplantation (FMT) has attracted significant interest. Network meta-analysis (NWM) has been established as an ...evidence-synthesis tool that incorporates direct and indirect evidence in a collection of randomized controlled trials (RCTs) comparing therapeutic intervention competing for similar therapeutic results. No NWM exists concerning the comparative effectiveness and safety of various FMT modalities for IBS.
We updated pairwise meta-analyses published in the past and assessed the comparative effectiveness and safety of various FMT delivery modalities for IBS.
Pairwise meta-analyses and Bayesian NWM were performed. Heterogeneity, consistency of results and publication bias were explored.
Of 510 titles raised by initial search, seven RCTs were entered into meta-analyses and NWM. They included 470 patients and controls, in whom four FMT delivery modalities were used, that is via colonoscopy, nasojejunal tube, duodenoscope and capsules per os. In the pairwise meta-analysis, the pooled results showed that overall FMT was not superior to placebo, whereas the subgroup analyses showed that FMT via duodenoscope and nasojejunal tube was superior. The NWM showed that 60-g FMT via duodenoscope had the highest efficacy (OR, 26.38; 95% CI, 9.22-75.51) and was by far the highest in the efficacy ranking (SUCRA, 98.8%).
The pooled results showed no overall advantage of FMT over placebo in IBS. However, upper GI delivery (via duodenoscopy or nasojejunal tube) proved to be effective. Consequently, well-designed RCTs are needed to ensure the efficacy and safety profile before FMT can be applied in everyday clinical practice for IBS patients.
IBD-what role do Proteobacteria play? Mukhopadhya, Indrani; Hansen, Richard; El-Omar, Emad M ...
Nature reviews. Gastroenterology & hepatology,
04/2012, Volume:
9, Issue:
4
Journal Article
Peer reviewed
The gastrointestinal microbiota has come to the fore in the search for the causes of IBD. This shift has largely been driven by the finding of genetic polymorphisms involved in gastrointestinal ...innate immunity (particularly polymorphisms in NOD2 and genes involved in autophagy) and alterations in the composition of the microbiota that might result in inflammation (so-called dysbiosis). Microbial diversity studies have continually demonstrated an expansion of the Proteobacteria phylum in patients with IBD. Individual Proteobacteria, in particular (adherent-invasive) Escherichia coli, Campylobacter concisus and enterohepatic Helicobacter, have all been associated with the pathogenesis of IBD. In this Review, we comprehensively describe the various associations of Proteobacteria and IBD. We also examine the importance of pattern recognition in the extracellular innate immune response of the host with particular reference to Proteobacteria, and postulate that Proteobacteria with adherent and invasive properties might exploit host defenses, drive proinflammatory change, alter the intestinal microbiota in favor of dysbiosis and ultimately lead to the development of IBD.
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