We tested the hypothesis that an altered community of gut microbes is associated with risk of colorectal cancer (CRC) in a study of 47 CRC case subjects and 94 control subjects. 16S rRNA genes in fecal bacterial DNA were amplified by universal primers, sequenced by 454 FLX technology, and aligned for taxonomic classification to microbial genomes using the QIIME pipeline. Taxonomic differences were confirmed with quantitative polymerase chain reaction and adjusted for false discovery rate. All statistical tests were two-sided. From 794217 16S rRNA gene sequences, we found that CRC case subjects had decreased overall microbial community diversity ( P = .02). In taxonomy-based analyses, lower relative abundance of Clostridia (68.6% vs 77.8%) and increased carriage of Fusobacterium (multivariable odds ratio [OR] = 4.11; 95% confidence interval [CI] = 1.62 to 10.47) and Porphyromonas (OR = 5.17; 95% CI = 1.75 to 15.25) were found in case subjects compared with control subjects. Because of the potentially modifiable nature of the gut bacteria, our findings may have implications for CRC prevention.

Oral microbiome dysbiosis is associated with oral disease and potentially with systemic diseases; however, the determinants of these microbial imbalances are largely unknown. In a study of 1204 US adults, we assessed the relationship of cigarette smoking with the oral microbiome. 16S rRNA gene sequencing was performed on DNA from oral wash samples, sequences were clustered into operational taxonomic units (OTUs) using QIIME and metagenomic content was inferred using PICRUSt. Overall oral microbiome composition differed between current and non-current (former and never) smokers (P<0.001). Current smokers had lower relative abundance of the phylum Proteobacteria (4.6%) compared with never smokers (11.7%) (false discovery rate q=5.2 × 10−7), with no difference between former and never smokers; the depletion of Proteobacteria in current smokers was also observed at class, genus and OTU levels. Taxa not belonging to Proteobacteria were also associated with smoking: the genera Capnocytophaga, Peptostreptococcus and Leptotrichia were depleted, while Atopobium and Streptococcus were enriched, in current compared with never smokers. Functional analysis from inferred metagenomes showed that bacterial genera depleted by smoking were related to carbohydrate and energy metabolism, and to xenobiotic metabolism. Our findings demonstrate that smoking alters the oral microbiome, potentially leading to shifts in functional pathways with implications for smoking-related diseases.

Increasing evidence suggests that the composition of the human gut microbiome is important in the etiology of human diseases; however, the personal factors that influence the gut microbiome composition are poorly characterized. Animal models point to sex hormone-related differentials in microbiome composition. In this study, we investigated the relationship of sex, body mass index (BMI) and dietary fiber intake with the gut microbiome in 82 humans. We sequenced fecal 16S rRNA genes by 454 FLX technology, then clustered and classified the reads to microbial genomes using the QIIME pipeline. Relationships of sex, BMI, and fiber intake with overall gut microbiome composition and specific taxon abundances were assessed by permutational MANOVA and multivariate logistic regression, respectively. We found that sex was associated with the gut microbiome composition overall (p=0.001). The gut microbiome in women was characterized by a lower abundance of Bacteroidetes (p=0.03). BMI (>25 kg/m² vs. <25 kg/m²) was associated with the gut microbiome composition overall (p=0.05), and this relationship was strong in women (p=0.03) but not in men (p=0.29). Fiber from beans and from fruits and vegetables were associated, respectively, with greater abundance of Actinobacteria (p=0.006 and false discovery rate adjusted q=0.05) and Clostridia (p=0.009 and false discovery rate adjusted q=0.09). Our findings suggest that sex, BMI, and dietary fiber contribute to shaping the gut microbiome in humans. Better understanding of these relationships may have significant implications for gastrointestinal health and disease prevention.

The esophagus, like other luminal organs of the digestive system, provides a potential environment for bacterial colonization, but little is known about the presence of a bacterial biota or its nature. By using broad-range 16S rDNA PCR, biopsies were examined from the normal esophagus of four human adults. The 900 PCR products cloned represented 833 unique sequences belonging to 41 genera, or 95 species-level operational taxonomic units (SLOTU); 59 SLOTU were homologous with culture-defined bacterial species, 34 with 16S rDNA clones, and two were not homologous with any known bacterial 16S rDNA. Members of six phyla, Firmicutes , Bacteroides , Actinobacteria , Proteobacteria , Fusobacteria , and TM7 , were represented. A large majority of clones belong to 13 of the 41 genera (783/900, 87%), or 14 SLOTU (574/900, 64%) that were shared by all four persons. Streptococcus (39%), Prevotella (17%), and Veilonella (14%) were most prevalent. The present study identified ≈56–79% of SLOTU in this bacterial ecosystem. Most SLOTU of esophageal biota are similar or identical to residents of the upstream oral biota, but the major distinction is that a large majority (82%) of the esophageal bacteria are known and cultivable. These findings provide evidence for a complex but conserved bacterial population in the normal distal esophagus.

Bacteria may play a role in esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (ESCC), although evidence is limited to cross-sectional studies. In this study, we examined the relationship of oral microbiota with EAC and ESCC risk in a prospective study nested in two cohorts. Oral bacteria were assessed using 16S rRNA gene sequencing in prediagnostic mouthwash samples from n = 81/160 EAC and n = 25/50 ESCC cases/matched controls. Findings were largely consistent across both cohorts. Metagenome content was predicted using PiCRUST. We examined associations between centered log-ratio transformed taxon or functional pathway abundances and risk using conditional logistic regression adjusting for BMI, smoking, and alcohol. We found the periodontal pathogen Tannerella forsythia to be associated with higher risk of EAC. Furthermore, we found that depletion of the commensal genus Neisseria and the species Streptococcus pneumoniae was associated with lower EAC risk. Bacterial biosynthesis of carotenoids was also associated with protection against EAC. Finally, the abundance of the periodontal pathogen Porphyromonas gingivalis trended with higher risk of ESCC. Overall, our findings have potential implications for the early detection and prevention of EAC and ESCC. Cancer Res; 77(23); 6777–87. ©2017 AACR.