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The gut microbiome has coevolved with humans to aid in physiologic functions and prevent disease. An increasing prevalence of gut dysbiosis in modern society exists and has strong linkages to multiple disease processes common in the developed world. Mechanisms for microbiome-human interactions that impact host homeostasis include bacterial metabolite/toxin production, biofilm formation with mucous layer infiltration, and host immune system modulation. Most of this crosstalk occurs at the epithelial layer of the gut, and as such the role of these interactions in the induction of colorectal cancer—a highly prevalent disease globally and one undergoing significant epidemiologic shifts—is under increasing scrutiny. Although multiple individual gut bacteria have been hypothesized as possible driver organisms in the oncogenic process, no bacterium has been definitively identified as a causal agent of colorectal cancer, suggesting that host lifestyle factors, microbiome community interactions, and the mucosal and/or systemic immune response may play a critical role in the process. Recent evidence has emerged implicating the ubiquitous human pathogen Clostridioides difficile as a possible promoter of colorectal cancer through chronic toxin-mediated cellular changes. Although much remains to be defined regarding the natural history of infections caused by this pathogen and its potential for oncogenesis, it provides a strong model for the role of both individual bacteria and of the gut microbial community as a whole in the development of colorectal cancer. The gut microbiome can play a crucial role in the development and prevention of human cancers through a variety of individual bacterial and broader community mechanisms. Emerging evidence suggests that Clostridioides difficile could be an important contributor to this balance. [ABSTRACT FROM AUTHOR]

Background Whether human immunodeficiency virus (HIV) infection impacts gut microbial α-diversity is controversial. We reanalyzed raw 16S ribosomal RNA (rRNA) gene sequences and metadata from published studies to examine α-diversity measures between HIV-uninfected (HIV–) and HIV-infected (HIV+) individuals. Methods We conducted a systematic review and individual level meta-analysis by searching Embase, Medline, and Scopus for original research studies (inception to 31 December 2017). Included studies reported 16S rRNA gene sequences of fecal samples from HIV+ patients. Raw sequence reads and metadata were obtained from public databases or from study authors. Raw reads were processed through standardized pipelines with use of a high-resolution taxonomic classifier. The χ2 test, paired t tests, and generalized linear mixed models were used to relate α-diversity measures and clinical metadata. Results Twenty-two studies were identified with 17 datasets available for analysis, yielding 1032 samples (311 HIV–, 721 HIV+). HIV status was associated with a decrease in measures of α-diversity (P <.001). However, in stratified analysis, HIV status was associated with decreased α-diversity only in women and in men who have sex with women (MSW) but not in men who have sex with men (MSM). In analyses limited to women and MSW, controlling for HIV status, women displayed increased α-diversity compared with MSW. Conclusions Our study suggests that HIV status, sexual risk category, and gender impact gut microbial community α-diversity. Future studies should consider MSM status in gut microbiome analyses. [ABSTRACT FROM AUTHOR]

Background The microbiome influences malaria parasite fitness and transmission efficiency in mosquitoes and appears to affect malaria dynamics in mammalian hosts as well. Nascent research examining the interrelationship of malaria and the mammalian microbiome has yielded interesting insights inviting further study. Methods We conducted a systematic review of the literature examining associations between the microbiome and malaria in mammalian hosts. An electronic search algorithm was adapted to PubMed, MEDLINE, Scopus, Embase, and Web of Science, and reference lists of relevant sources were manually searched. Identified studies were screened and assessed independently by 2 authors, and results were compiled in a qualitative synthesis of the evidence. Results Ten relevant studies were identified. They demonstrate associations between certain intestinal communities and protection against Plasmodium infection and modulation of disease severity. Plasmodium infection acutely and reversibly reshapes gut microbial composition in mice. The makeup of human skin microbial communities may influence mosquito attraction and thus disease transmission. Conclusions Early research supports a relationship between malaria and the microbiome. The evidence is incomplete, but the observed associations are evocative and signal a promising avenue of inquiry. Microbiome-based studies of malaria can be readily integrated into field-based research. [ABSTRACT FROM AUTHOR]

Microbial exposures are crucial environmental factors that impact healthspan by sculpting the immune system and microbiota. Antibody profiling via Phage ImmunoPrecipitation Sequencing (PhIP-Seq) provides a high-throughput, cost-effective approach for detecting exposure and response to microbial protein products. We designed and constructed a library of 95,601 56-amino acid peptide tiles spanning 14,430 proteins with "toxin" or "virulence factor" keyword annotations. We used PhIP-Seq to profile the antibodies of ∼1,000 individuals against this "ToxScan" library. In addition to enumerating immunodominant antibody epitopes, we studied the age-dependent stability of the ToxScan profile and used a genome-wide association study to find that the MHC-II locus modulates bacterial epitope selection. We detected previously described anti-flagellin antibody responses in a Crohn's disease cohort and identified an association between anti-flagellin antibodies and juvenile dermatomyositis. PhIP-Seq with the ToxScan library is thus an effective tool for studying the environmental determinants of health and disease at cohort scale. [Display omitted] • ToxScan phage library covers >14k toxins and virulence factors for antibody profiling • Serum antibody binding to ToxScan peptides is unique and stable in adulthood • MHC-II locus influences toxin and/or virulence factor antibody epitope selection • Crohn's-disease-associated flagellin antibodies are also found in juvenile dermatomyositis Lifelong exposures to microbes and their protein products profoundly impact human health. Angkeow et al. employed pan-toxin, pan-virulence factor PhIP-Seq to profile the antibodies of healthy volunteers and patients with autoinflammatory diseases. They report that peptide binding repertoires are unique and stable in adulthood and are modulated by the MHC-II locus. Crohn's-disease-associated flagellin antibodies are found in juvenile dermatomyositis patients. [ABSTRACT FROM AUTHOR]

Background Microbiome dysbiosis predisposes to colorectal cancer (CRC), but a population-based study of oral antibiotic exposure and CRC risk is lacking. Methods A matched case–control study (incident CRC cases and up to 5 matched controls) was conducted in the Clinical Practice Research Datalink (CPRD; 1989–2012). The CRPD is validated as 92% and 99% sensitive and specific for CRC detection (98% PPV). Antibiotic exposure [categorical and continuous terms (spline)] was investigated for risk pattern, stratified by tumor location, using conditional logistic regression and adjusting for known confounders. Results In total, 28,980 CRC cases and 137,077 controls were identified. Oral antibiotic use increased risk of colon cancer in a dose-dependent fashion (P trend < 0.001), but effects differed by anatomic location. Colon cancer risk was greatest in the proximal colon and with antibiotics with anti-anaerobic activity (Figure 1). In contrast, an inverse association was detected between antibiotic use and rectal cancers (P trend = 0.003), particularly with length of antibiotic exposure >60 days (adjusted odds ratio [AOR], 0.85, 95% CI 0.79–0.93) when compared with no antibiotic exposure. Nonlinearity models showed significantly increased colon cancer risk after minimal antibiotic use, but decreased rectum cancer risk with cumulative use of over 30 days (Figure 2). Penicillins, particularly ampicillin/amoxicillin, increased risk of colon cancer (AOR,1.09, [1.05–1.13]) whereas tetracyclines reduced risk for rectal cancer (AOR, 0.90, [0.84–0.97]). Significant interactions were detected between antibiotic use and tumor location (colon vs. rectum, P interaction < 0.001). The antibiotic-cancer association was found for antibiotic exposure occurring >10 years before diagnosis (AOR, 1.17, [1.06–1.31]). Conclusion We conclude that oral antibiotic use associates with increased colon cancer risk, particularly in the right colon, but a reduced risk for rectal cancer. This effect heterogeneity suggests unabsorbed antibiotics impact gut microbiota in the right colon to enhance carcinogenesis whereas antibiotic anti-inflammatory or anti-proliferative actions may yield an inverse effect on carcinogenesis in the rectum. Disclosures Sara E. Cosgrove, MD, MS, Basilea: Consultant; Theravance: Consultant. [ABSTRACT FROM AUTHOR]