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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.

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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.

Key historical barriers to FMT access include regulatory uncertainty, operational complexity of sourcing screened donor material, and logistical challenges of delivering fresh treatment preparations. USBs have demonstrated that FMT can be delivered safely at scale by centralizing donor selection, material processing, and safety monitoring. More evidence is needed to optimize USB methods, including for donor screening, material processing, and novel delivery modalities. USBs have catalyzed broad access to FMT in North America and Europe. Future directions include developing evidence regarding oral preparations, harmonizing guidelines, disseminating best practice protocols, establishing long-term safety profiles, and expanding access to geographic areas of unmet need.

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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.

IntroductionCompared 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.MethodsWe 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.ResultsWe 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.ConclusionFuture studies should include combinations of proven methods for engaging adolescents in HIV testing, while ensuring effective methods of linkage to care.