Fecal transplantation for ulcerative colitis from diet conditioned donors followed by dietary intervention results in favorable gut microbial profile compared to fecal transplantation alone.

BACKGROUND AND AIMS: Several fecal microbial transplantation (FMT) approaches for ulcerative colitis (UC) have been investigated with conflicting results. We have recently published the clinical outcomes from the CRAFT-UC Trial using FMT with the UC Exclusion Diet (UCED), compared with FMT alone. Here we aimed to compare the two FMT strategies in terms of microbial profile and function. METHODS: Subjects recruited to the CRAFT-UC study with available pre- and post-intervention fecal samples were included. Donors received diet conditioning for 14 days based on the UCED principles. Group-1 received single FMT by colonoscopy (Day 1) and enemas (Days 2 and 14) without donors' dietary conditioning (N=11). Group-2 received FMT but with donors' dietary pre-conditioning and UCED for the patients (N=10). Fecal samples were assessed by DNA shotgun metagenomic sequencing. RESULTS: Following diet conditioning, donors had depletion in metabolic pathways involved in sulfur-containing amino acids biosynthesis. Only Group-2 showed significant shifts towards the donors' microbial composition (ADONIS: R2=0.15, p=0.008) and significant increased Eubacterium_sp_AF228LB post-intervention (ß-coefficient 2.66, 95%CI 2.1-3.3, q<0.05) which was inversely correlated with fecal calprotectin (rho=-0.52, p=0.035). Moreover, pathways involved in gut inflammation and barrier function including branched chain amino acids were enriched post intervention in Group-2 and were significantly inversely correlated with fecal calprotectin. CONCLUSION: FMT from diet conditioned donors followed by the UCED led to microbial alterations associated with favorable microbial profile which correlated with decreased fecal calprotectin. Our findings support further exploration of additive benefit of dietary intervention for both donors and patients undergoing FMT as a potential treatment of UC.

Use of Faecal Transplantation with a Novel Diet for Mild to Moderate Active Ulcerative Colitis: The CRAFT UC Randomised Controlled Trial.

BACKGROUND: We evaluated whether integration of novel diets for donors and patients, in addition to faecal transplantation [FT], could increase FT remission rate in refractory ulcerative colitis [UC]. METHODS: This was a blinded, randomised, controlled trial in adults with active UC, defined by a simple clinical colitis activity index [SCCAI] of ≥5 and ≤11 and endoscopic Mayo score 2-3, refractory to medication. Group 1 received free diet and single donor standard FT by colonoscopy on Day 1and rectal enemas on Days 2 and 14 without dietary conditioning of the donor. Group 2 received FT as above but with dietary pre-conditioning of the donor for 14 days and a UC Exclusion Diet [UCED] for the patients. Group 3 received the UCED alone. The primary endpoint was Week 8 clinical steroid-free remission, defined as SCCAI <3. RESULTS: Of 96 planned patients, 62 were enrolled. Remission Week 8 Group 1 was 2/17 [11.8%], Group 2 was 4/19 [21.1%], Group 3 was 6/15 [40%] [non-significant]. Endoscopic remission Group 1 was 2/17 [12%], Group 2 was 3/19 [16%], Group 3 was 4/15 [27%] [Group 1 vs 3 p = 0.38]. Mucosal healing [Mayo 0] was achieved only in Group 3 [3/15, 20%] vs 0/36 FT patients [p = 0.022]. Exacerbation of disease occurred in 3/17 [17.6%] of Group 1, 4/19 [21.1%] of Group 2, and 1/15 [6.7%] of Group 3 [Group 2 vs 3, p = 0.35]. CONCLUSIONS: UCED alone appeared to achieve higher clinical remission and mucosal healing than single donor FT with or without diet. The study was stopped for futility by a safety monitoring board.

Normal response to vaccines in inflammatory bowel disease patients treated with thiopurines.

BACKGROUND: Thiopurines are considered immunosuppressive agents and may be associated with an increased risk for infections. However, few inflammatory bowel disease (IBD) patients are appropriately vaccinated, and data on their ability to mount an immune response are vague. We evaluated the effects of the thiopurines, azathioprine (AZA) and 6-mercaptopurine (6-MP), on cellular and humoral immune responses in IBD patients. METHODS: A prospective clinical investigation was conducted on IBD patients referred for thiopurine treatment. Immune competence was evaluated by assessing lymphocyte counts and phenotype, response to mitogen and antigen stimulation, immunoglobulin levels, and response to pneumococcal and tetanus vaccines (before treatment, week 0), and to Haemophilus influenza type b vaccine (at week 24). RESULTS: Thirty-one Crohn's disease and 12 ulcerative colitis patients who completed at least 24 weeks of therapy were included. The posttherapy average 6-MP dose was 1.05 ± 0.30 mg/kg, and white blood cell counts had decreased significantly from baseline values (P < 0.002). The posttreatment response to mitogens and antigens and the immunoglobulin levels were unchanged. Responses to vaccines were normal both in thiopurine-naïve and thiopurine-treated patients, suggesting that these patients were immunologically intact while on thiopurine therapy and capable of generating normal immune responses in vivo. CONCLUSIONS: There is no evidence for any intrinsic systemic immunodeficiency in IBD patients. Thiopurines at the doses used for treating IBD showed no significant suppressive effect on the systemic cellular and humoral immune responses evaluated. Thiopurine-treated IBD patients can be safely and efficiently vaccinated.

Celiac disease diagnosed in the elderly.

BACKGROUND AND AIMS: In the past 20 years, a growing proportion of new cases of celiac disease (CD) are diagnosed in adults and in patients with extraintestinal manifestations. Our understanding of the extremely wide spectra of manifestations and the profound effects on elderly patients is improving. Nevertheless, CD is still underdiagnosed in elderly patients. In this study, we describe a case series of CD patients diagnosed after the age of 60. METHODS: A retrospective chart review was preformed in cases of CD diagnosed after the age of 60. Patients were included if they had positive serology and histologic findings compatible with CD. Eligible patients were reinterviewed, and demographic, clinical, and laboratory information were recorded. RESULTS: During the study period, 7 patients with CD diagnosed after the age of 60 were identified. The most common presenting findings were weight loss, iron deficiency anemia, and diarrhea. Two patients suffered from severe early osteoperosis and 2 additional patients had elevated liver function tests. Neurologic manifestation was suspected in 3 cases. Two female patients presented with cognitive decline that was attributed to Alzheimer dementia but ameliorated after the initiation of gluten-free diet. The third patient had peripheral neuropathy that completely resolved after the initiation of gluten-free diet. Median lag in diagnosis was 8 years. Diet treatment led to complete resolution of symptoms in most cases and a significant weight gain (median 7.75 kg, range 5 to 11). One patient developed a fatal intestinal T-cell lymphoma. CONCLUSIONS: In this case series, we have described several cases of CD in patients over the age of 60 with a varied spectrum of manifestations. We have also found a significant lag in diagnosis and treatment. We believe that it is important to promote the identification of CD as a possible culprit in varied clinical conditions in the elderly population.