Faculty Bibliography

Increasing 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.

BACKGROUND: Colorectal cancer is a heterogeneous disease arising from at least two precursors-the conventional adenoma (CA) and the serrated polyp. We and others have previously shown a relationship between the human gut microbiota and colorectal cancer; however, its relationship to the different early precursors of colorectal cancer is understudied. We tested, for the first time, the relationship of the gut microbiota to specific colorectal polyp types. RESULTS: Gut microbiota were assessed in 540 colonoscopy-screened adults by 16S rRNA gene sequencing of stool samples. Participants were categorized as CA cases (n = 144), serrated polyp cases (n = 73), or polyp-free controls (n = 323). CA cases were further classified as proximal (n = 87) or distal (n = 55) and as non-advanced (n = 121) or advanced (n = 22). Serrated polyp cases were further classified as hyperplastic polyp (HP; n = 40) or sessile serrated adenoma (SSA; n = 33). We compared gut microbiota diversity, overall composition, and normalized taxon abundance among these groups. CA cases had lower species richness in stool than controls (p = 0.03); in particular, this association was strongest for advanced CA cases (p = 0.004). In relation to overall microbiota composition, only distal or advanced CA cases differed significantly from controls (p = 0.02 and p = 0.002). In taxon-based analysis, stool of CA cases was depleted in a network of Clostridia operational taxonomic units from families Ruminococcaceae, Clostridiaceae, and Lachnospiraceae, and enriched in the classes Bacilli and Gammaproteobacteria, order Enterobacteriales, and genera Actinomyces and Streptococcus (all q < 0.10). SSA and HP cases did not differ in diversity or composition from controls, though sample size for these groups was small. Few taxa were differentially abundant between HP cases or SSA cases and controls; among them, class Erysipelotrichi was depleted in SSA cases. CONCLUSIONS: Our results indicate that gut microbes may play a role in the early stages of colorectal carcinogenesis through the development of CAs. Findings may have implications for developing colorectal cancer prevention therapies targeting early microbial drivers of colorectal carcinogenesis.

BACKGROUND: We sought to study the clinicopathologic characteristics of colorectal cancer in young female patients. We also wanted to determine the association of colorectal cancer with anemia in these female patients and, finally, to determine the effect of gender on prognosis in young patients with colorectal cancer. METHODS: We performed a retrospective analysis of all young patients diagnosed with colorectal cancer between 1982 and 1999 in two teaching hospitals in New York City. RESULTS: A total of 3,546 cases of colorectal cancer were diagnosed. Sixty-one (1.63%) of these patients were young patients and 32 (0.85%) were female. Young refers to all patients in the study who were younger than 40 years of age. The clinical presentation and mean age at presentation were very similar in both male and female patients. At presentation, 87.5% of female patients had anemia compared with only 69% of male patients. Males had a statistically significant higher mean hemoglobin level compared with females (12.87 versus 10.29 g) at P = 0.0001. Seventy-nine percent of female patients compared with 86% of male patients presented with left-sided tumors. Fifty-five percent of males presented with late stage disease compared with 68% of females (P = 0.27). Female sex seemed to adversely affect the prognosis, although this did not reach statistical significance (P = 0.08). Stage of disease was associated with worse prognosis and this was independent of sex. Age and hemoglobin were not independent predictors of mortality. CONCLUSION: Colorectal cancer does occur in females of childbearing age who might have a tendency to present with late stage disease as evidence from this study. Young female patients with anemia should be questioned about gastrointestinal symptoms, and colorectal cancer should definitely be in the differential diagnoses. This might conceivably allow for earlier diagnosis and potential for cure in this patient group

The cholangiographic and pancreatographic appearances of the acquired immunodeficiency syndrome (AIDS) associated cholangitis were evaluated in 26 patients. Twenty-four patients were diagnosed by retrograde cholangiography or endoscopic cholangiopancreatography (ERC or ERCP). One patient was diagnosed by T-tube cholangiography and another patient by transhepatic cholangiography. The radiographic findings ranged from intrahepatic ductal abnormalities with or without involvement of the extrahepatic biliary tree (eight patients) to irregularities and strictures involving the ampulla of Vater or the intrapancreatic portion of the common bile duct (CBD) with proximal dilatation (18 patients). Significant strictures involving the juxta-ampullary pancreatic duct were identified in six of 12 patients. Twenty-one of the 26 patients had associated infections which included: Cryptosporidium (CS), Mycobacterium avium intracellulare (MAI), cytomegalovirus (CMV), Microsporidium (MSP), and Isospora (ISP). Three patients were operated upon for acute acalculous cholecystitis. In each instance, organisms were identified in both the bile duct and the inflamed gallbladder.