INTRODUCTION: Nonalcoholic fatty liver disease (NAFLD) is an obesity-related disorder that is rapidly increasing in incidence and is considered the hepatic manifestation of the metabolic syndrome. The gut microbiome plays a role in metabolism and maintaining gut barrier integrity. Studies have found differences in the microbiota between NAFLD and healthy patients and increased intestinal permeability in patients with NAFLD. Fecal microbiota transplantation (FMT) can be used to alter the gut microbiome. It was hypothesized that an FMT from a thin and healthy donor given to patients with NAFLD would improve insulin resistance (IR), hepatic proton density fat fraction (PDFF), and intestinal permeability. METHODS: Twenty-one patients with NAFLD were recruited and randomized in a ratio of 3:1 to either an allogenic (n = 15) or an autologous (n = 6) FMT delivered by using an endoscope to the distal duodenum. IR was calculated by HOMA-IR, hepatic PDFF was measured by MRI, and intestinal permeability was tested using the lactulose:mannitol urine test. Additional markers of metabolic syndrome and the gut microbiota were examined. Patient visits occurred at baseline, 2, 6 weeks, and 6 months post-FMT. RESULTS: There were no significant changes in HOMA-IR or hepatic PDFF in patients who received the allogenic or autologous FMT. Allogenic FMT patients with elevated small intestinal permeability (>0.025 lactulose:mannitol, n = 7) at baseline had a significant reduction 6 weeks after allogenic FMT. DISCUSSION: FMT did not improve IR as measured by HOMA-IR or hepatic PDFF but did have the potential to reduce small intestinal permeability in patients with NAFLD.

Dendritic cells (DCs) have a central role in the initiation and regulation of immune responses in both lymphoid and nonlymphoid tissues. They share a number of common features, notably MHC class II expression, in combination with an absence of the lineage-specific markers CD3, CD14, CD16, and CD19 (lin Ϫ ). [1][2][3] There is however considerable intra-and intertissue variation in the phenotype, morphology, function, and tissue localization of different DC populations. [1][2][3][4][5][6][7] After the identification of distinct myeloid DC and lymphoid DC subsets in mice 3 there has been increasing interest in the characterization of human DC subsets. These have been categorized on the basis of differential expression of myeloid and lymphoid lineage-associated markers, as well as their responsiveness to maturation or differentiation stimuli. 8 -13 There is evidence that myeloid DCs and lymphoid DCs direct immunogenic and tolerogenic responses, respectively. 13 It is unclear whether human DC subsets represent distinct cell lineages 10,12 or differing maturation states. 9,14 As a result, the ontogeny and interrelationship of human DC subsets requires further investigation.Tonsils have been used as a readily available source of lymphoid tissue to characterize human DCs. 15 Three tonsil DC subsets have been identified: interdigitating DCs (IDCs), 16 plasmacytoid DCs, 17 and germinal center DCs (GCDCs). 18 These DC subsets were isolated after a period of in vitro culture, which is likely to alter cell phenotype and morphology. 19 They were also positively selected from lin Ϫ cells based on their expression of the CD4, CD11c, or CD40 antigens, which would exclude any DC subsets lacking these antigens and would incorporate all DC subsets expressing those antigens into one population. The observation that both IDCs and GCDCs were heterogeneous with regard to CD11c, CD83, HLA-DR, and CD13 intensity raised the possibility that these tonsil DC populations might contain additional subsets. This is the first study to analyze the composition of tonsil DC subsets within the entire lin Ϫ HLA-DR ϩ DC population isolated using a new method that maintains the cells at 4°C to minimize changes in cellular differentiation/activation induced by the isolation procedure. We report the presence of five distinct DC subsets within human tonsils. The phenotype of each tonsil DC subset was analyzed by threecolor flow cytometry and two-color immunohistochemistry using an extensive panel of antigens relevant to DC lineage, activation state, and function. Materials and Methods Patients and SamplesAfter approval by the Canterbury Ethics Committee and appropriate informed consent, tonsils were obtained from 68 patients undergoing routine tonsillectomies, which were excised in a noninflamed state. They were trans-

Sitagliptin does not improve fibrosis score or NAS after 24 wk of therapy. The MRI IDEAL technique may be useful for non-invasive measurement of hepatic steatosis.

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