Background. Fecal microbiota transplantation (FMT) is an effective treatment of recurrent Clostridioides difficile infections (rCDI), but has more limited efficacy in treating either ulcerative colitis (UC) or Crohn’s disease (CD), two major forms of inflammatory bowel diseases (IBD). We hypothesize that FMT recipients with rCDI and/or IBD have baseline fecal bile acid (BA) compositions that differ significantly from that of their healthy donors and that FMT will normalize the BA compositions. Aim. To study the effect of single colonoscopic FMT on microbial composition and function in four recipient groups: 1.) rCDI patients without IBD (rCDI-IBD); 2.) rCDI with IBD (rCDI+IBD); 3.) UC patients without rCDI (UC-rCDI); 4.) CD patients without rCDI (CD-rCDI). Methods. We performed 16S rRNA gene sequence, shotgun DNA sequence and quantitative bile acid metabolomic analyses on stools collected from 55 pairs of subjects and donors enrolled in two prospective single arm FMT clinical trials (Clinical Trials.gov ID NCT03268213, 479696, UC no rCDI ≥ 2x IND 1564 and NCT03267238, IND 16795). Fitted linear mixed models were used to examine the effects of four recipient groups, FMT status (Donor, pre-FMT, 1-week post-FMT, 3-months post-FMT) and first order Group*FMT interactions on microbial diversity and composition, bile acid metabolites and bile acid metabolizing enzyme gene abundance. Results. The pre-FMT stools collected from rCDI ± IBD recipients had reduced α-diversity compared to the healthy donor stools and was restored post-FMT. The α-diversity in the pre-FMT stools collected from UC-rCDI or CD-rCDI recipients did not differ significantly from donor stools. FMT normalized some recipient/donor ratios of genus level taxa abundance in the four groups. Fecal secondary BA levels, including some of the secondary BA epimers that exhibit in vitro immunomodulatory activities, were lower in rCDI±IBD and CD–rCDI but not UC-rCDI recipients compared to donors. FMT restored secondary BA levels. Metagenomic baiE gene and some of the eight bile salt hydrolase (BSH) phylotype abundances were significantly correlated with fecal BA levels. Conclusion. Restoration of multiple secondary BA levels, including BA epimers implicated in immunoregulation, are associated with restoration of fecal baiE gene counts, suggesting that the 7-α-dehydroxylation step is rate-limiting.
Pancreatic cancer is characterized by aggressive growth and resistance to treatment. Identification of unique biomarkers for diagnosis and prognosis is important for treatment of this disease. We investigated the expression patterns of mucin 1 (MUC1), mucin 2 (MUC2) and cytokeratin 17 (CK17) in both normal tissues and metastatic adenocarcinomas using immunohistochemistry (IHC). We have shown that MUC1 (pan-epithelial membrane mucin), MUC2 (intestinal-type secretory mucin) and CK17 can be used as a panel of markers to distinguish collectively pancreatobiliary carcinoma from other primary site carcinomas. Tumors originating in the pancreatobiliary system showed an expression pattern of MUC1 (+), MUC2 (-) and CK17 (+). By contrast, tumors arising from the colorectal region were MUC1 (-), MUC2 (+) and CK17 (-), while tumors originating from non-pancreatobiliary system tissue expressed a MUC1 (+), MUC2 (-) and CK17 (-) profile. More importantly, the MUC1 (+), MUC2 (-) and CK17 (+) result showed greater sensitivity than CA19-9 by IHC, which is the currently accepted and widely used pancreatic tumor marker for diagnosing pancreatic cancer. Thirteen of 51 cases (25%) of pancreatobiliary adenocarcinomas with the pattern MUC1 (+), MUC2 (-) and CK17 (+) showed no immunoreactivity for CA19-9, while 34/51 (67%) cases having MUC1 (+), MUC2 (-) and CK17 (+) were correlated with positive CA19-9 staining. Our data support using an antibody panel of MUC1, MUC2 and CK17 to enhance current methods for pancreatic cancer diagnosis by identifying specifically the primary tissue of origin.
BACKGROUND The Black/African Ancestry (AA) population has a higher prevalence of type 2 diabetes mellitus (T2DM) and a higher incidence and mortality rate for colorectal cancer (CRC) than all other races in the United States. T2DM has been shown to increase adenoma risk in predominantly white/European ancestry (EA) populations, but the effect of T2DM on adenoma risk in Black/AA individuals is less clear. We hypothesize that T2DM has a significant effect on adenoma risk in a predominantly Black/AA population. AIM To investigate the effect of T2DM and race on the adenoma detection rate (ADR) in screening colonoscopies in two disparate populations. METHODS A retrospective cohort study was conducted on ADR during index screening colonoscopies (age 45-75) performed at an urban public hospital serving a predominantly Black/AA population (92%) (2017-2018, n = 1606). Clinical metadata collected included basic demographics, insurance, body mass index (BMI), family history of CRC, smoking, diabetes diagnosis, and aspirin use. This dataset was combined with a recently reported parallel retrospective cohort data set collected at a suburban university hospital serving a predominantly White/EA population (87%) (2012-2015, n = 2882). RESULTS The ADR was higher in T2DM patients than in patients without T2DM or prediabetes (35.2% vs 27.9%, P = 0.0166, n = 981) at the urban public hospital. Multivariable analysis of the combined datasets showed that T2DM [odds ratio (OR) = 1.29, 95% confidence interval (CI): 1.08-1.55, P = 0.0049], smoking (current vs never OR = 1.47, 95%CI: 1.18-1.82, current vs past OR = 1.32, 95%CI: 1.02-1.70, P = 0.0026 ) , older age (OR = 1.05 per year, 95%CI: 1.04-1.06, P < 0.0001), higher BMI (OR = 1.02 per unit, 95%CI: 1.01-1.03, P = 0.0003), and male sex (OR = 1.87, 95%CI: 1.62-2.15, P < 0.0001 ) were associated with increased ADR in the combined datasets, but race, aspirin use and insurance were not. CONCLUSION T2DM, but not race, is significantly associated with increased ADR on index screening colonoscopy while controlling for other factors.
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