Daily, oral FMT for long-term maintenance therapy in ulcerative colitis: results of a single-center, prospective, randomized pilot study.

BACKGROUND: Fecal microbiota transplantation (FMT) is a promising new strategy in the treatment of Inflammatory Bowel Disease, but long-term delivery systems are lacking. This randomized study was designed as a safety and feasibility study of long-term FMT in subjects with mild to moderate UC using frozen, encapsulated oral FMT (cFMT). METHODS: Subjects were randomized 1:1 to receive FMT induction by colonoscopy, followed by 12 weeks of daily oral administration of frozen encapsulated cFMT or sham therpay. Subjects were followed for 36 weeks and longitudenal clinical assessments included multiple subjective and objective markers of disease severity. Ribosomal 16S bacterial sequencing was used to assess donor-induced changes in the gut microbiota. Changes in T regulatory (Treg) and mucosal associated invariant T (MAIT) cell populations were evaluated by flow cytometry as an exploratory endpoint. RESULTS: Twelve subjects with active UC were randomized: 6 subjects completed the full 12-week course of FMT plus cFMT, and 6 subjects received sham treatment by colonic installation and longitudinal oral placebo capules. Chronic administration of cFMT was found to be safe and well-tolerated but home storage concerns exist. Protocol adherence was high, and none of the study subjects experienced FMT-associated treatment emergent adverse events. Two subjects that received cFMT achieved clinical remission versus none in the placebo group (95% CI = 0.38-infinity, p = 0.45). cFMT was associated with sustained donor-induced shifts in fecal microbial composition. Changes in MAIT cell cytokine production were observed in cFMT recipients and correlated with treatment response. CONCLUSION: These pilot data suggest that daily encapsulated cFMT may extend the durability of index FMT-induced changes in gut bacterial community structure and that an association between MAIT cell cytokine production and clinical response to FMT may exist in UC populations. Oral frozen encapsulated cFMT is a promising FMT delivery system and may be preferred for longterm treatment strategies in UC and other chronic diseases but further evaluations will have to address home storage concerns. Larger trials should be done to explore the benefits of cFMT and to determine its long-term impacts on the colonic microbiome. TRIAL REGISTRATION: ClinicalTrials.gov (NCT02390726). Registered 17 March 2015, https://clinicaltrials.gov/ct2/show/NCT02390726?term=NCT02390726&draw=2&rank=1 .

Fecal microbiota transplantation in HIV: A pilot placebo-controlled study.

Changes in the microbiota have been linked to persistent inflammation during treated HIV infection. In this pilot double-blind study, we study 30 HIV-infected subjects on antiretroviral therapy (ART) with a CD4/CD8 ratio < 1 randomized to either weekly fecal microbiota capsules or placebo for 8 weeks. Stool donors were rationally selected based on their microbiota signatures. We report that fecal microbiota transplantation (FMT) is safe, not related to severe adverse events, and attenuates HIV-associated dysbiosis. FMT elicits changes in gut microbiota structure, including significant increases in alpha diversity, and a mild and transient engraftment of donor's microbiota during the treatment period. The greater engraftment seems to be achieved by recent antibiotic use before FMT. The Lachnospiraceae and Ruminococcaceae families, which are typically depleted in people with HIV, are the taxa more robustly engrafted across time-points. In exploratory analyses, we describe a significant amelioration in the FMT group in intestinal fatty acid-binding protein (IFABP), a biomarker of intestinal damage that independently predicts mortality. Gut microbiota manipulation using a non-invasive and safe strategy of FMT delivery is feasible and deserves further investigation. Trial number: NCT03008941.

Faecal microbiota transplantation for diarrhoea-predominant irritable bowel syndrome: a double-blind, randomised, placebo-controlled trial.

BACKGROUND: Faecal microbiota transplantation (FMT) has shown promise in alleviating the symptoms of irritable bowel syndrome (IBS); however, controlled data on this technique are scarce. The aim of this clinical trial was to assess the efficacy of FMT in alleviating diarrhoea-predominant IBS (IBS-D). METHODS: We did a double-blind, randomised, placebo-controlled crossover trial in patients aged 18-65 years with moderate-to-severe IBS-D defined by an IBS-Symptom Severity Score (IBS-SSS) of more than 175, recruited from three US centres. Patients were randomly assigned (1:1) in blocks of four with a computer-generated randomisation sequence to receive FMT capsules followed by identical-appearing placebo capsules, or placebo capsules followed by FMT capsules. All participants and study team members were masked to randomisation. An independent staff member assigned the treatments according to consecutive numbers. Patients received either 75 FMT capsules (each capsule contained approximately 0·38 g of minimally processed donor stool) or 75 placebo capsules over 3 days (25 capsules per day). All patients crossed over to the alternate treatment at 12 weeks. The primary outcome was difference in IBS-SSS between the groups at 12 weeks. Intention-to-treat analyses were done and all patients who received study drug were included in an adverse events analysis. The trial was terminated during recruitment because results from an interim analysis revealed futility. The study is registered with ClinicalTrials.gov, number NCT02328547. FINDINGS: From May 28, 2015, to April 21, 2017, 48 patients were randomly assigned to receive FMT first (n=25) or placebo first (n=23). Three participants were lost to follow-up in the FMT group. IBS-SSS did not differ between FMT recipients (mean 221 [SD 105]) and placebo recipients (236 [95]) at 12 weeks (p=0·65), after adjustment for baseline scores. The most common drug-related adverse events included abdominal pain (five [10%] of the 48 participants while receiving FMT capsules vs four [8%] while receiving placebo), nausea (four [8%] vs two [4%]), and exacerbation of diarrhoea (three [6%] vs eight [17%]). One serious adverse event that was unrelated to study drug (acute cholecystitis) was reported in a patient while receiving placebo capsules. INTERPRETATION: FMT was safe, but did not induce symptom relief at 12 weeks compared with placebo. Additional studies are needed to determine the efficacy of FMT for IBS-D. FUNDING: National Institutes of Health.

Screening for HIV and linkage to care in adolescents: insights from a systematic review of recent interventions in high- versus low- and middle-income settings.

INTRODUCTION: Compared to adults, adolescents and young adults have a higher incidence of HIV infection, yet lower rates of HIV testing. Few evidence-based interventions effectively diagnose new HIV infections among adolescents while successfully providing linkage to care. METHODS: We conducted a systematic review of recent interventions to increase HIV testing among adolescents and young adults using data retrieved from PubMed and Google Scholar, and using abstracts presented at the International AIDS Society conferences and Conference on Retroviruses and Opportunistic Infections published between January 1, 2015, and April 28, 2018. RESULTS: We identified 36 interventions (N=14 in high- income countries and N=22 in low- and middle-income countries) that were published in the literature (N=28) or presented at conferences (N=8). Interventions were categorized as behavioral/educational, alternate venue/self-testing, youth-friendly services, technology/mobile health, incentives, or peer-based/community-based interventions. The studies consisted of randomized controlled trials (RCTs), prospective and retrospective observational studies, and quasi-experimental/pre-post evaluations with variable sample sizes. Study designs, populations, and settings varied. All categories showed some degree of acceptability, yet not all interventions were effective in increasing HIV testing. Effectiveness was seen in more than one RCT involving technology/mobile health (2/3 RCTs) and alternative venue/self-testing (3/3 RCTs) interventions, and only in one RCT each for behavioral interventions, community interventions, and incentives. There were no effective RCTs for adolescent-friendly services. Data were limited on the number of new infections identified and on the methods to increase linkage to care after diagnosis. CONCLUSION: Future studies should include combinations of proven methods for engaging adolescents in HIV testing, while ensuring effective methods of linkage to care.

Intestinal Microbial and Metabolic Alterations Following Successful Fecal Microbiota Transplant for D-Lactic Acidosis.

Fecal microbiota transplantation (FMT) involves the transfer of stool from a healthy individual into the intestinal tract of a diseased recipient. Although used primarily for recurrent Clostridium difficile infection, FMT is increasingly being attempted as an experimental therapy for other illnesses, including metabolic disorders. D-lactic acidosis (D-LA) is a metabolic disorder that may occur in individuals with short bowel syndrome when lactate-producing bacteria in the colon overproduce D-lactate. This results in elevated systemic levels of D-lactate, metabolic acidosis, and encephalopathy. In this study, we report the successful use of FMT for the treatment of recurrent D-LA in a child who was unresponsive to conventional therapies. Importantly, we also present profiles of the enteric microbiota, as well as fecal D-/L-lactic acid metabolites, before and longitudinally after FMT. These data provide valuable insight into the putative mechanisms of D-LA pathogenesis and its treatment.

Trypanosoma cruzi-Trypanosoma rangeli co-infection ameliorates negative effects of single trypanosome infections in experimentally infected Rhodnius prolixus.

Trypanosoma cruzi, causative agent of Chagas disease, co-infects its triatomine vector with its sister species Trypanosoma rangeli, which shares 60% of its antigens with T. cruzi. Additionally, T. rangeli has been observed to be pathogenic in some of its vector species. Although T. cruzi-T. rangeli co-infections are common, their effect on the vector has rarely been investigated. Therefore, we measured the fitness (survival and reproduction) of triatomine species Rhodnius prolixus infected with just T. cruzi, just T. rangeli, or both T. cruzi and T. rangeli. We found that survival (as estimated by survival probability and hazard ratios) was significantly different between treatments, with the T. cruzi treatment group having lower survival than the co-infected treatment. Reproduction and total fitness estimates in the T. cruzi and T. rangeli treatments were significantly lower than in the co-infected and control groups. The T. cruzi and T. rangeli treatment group fitness estimates were not significantly different from each other. Additionally, co-infected insects appeared to tolerate higher doses of parasites than insects with single-species infections. Our results suggest that T. cruzi-T. rangeli co-infection could ameliorate negative effects of single infections of either parasite on R. prolixus and potentially help it to tolerate higher parasite doses.