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Background & aimsStudies investigating the gut-liver axis have largely focused on bacteria, whereas little is known about commensal fungi. We characterized fecal fungi in patients with non-alcoholic fatty liver disease (NAFLD) and investigated their role in a fecal microbiome-humanized mouse model of Western diet-induced steatohepatitis.MethodsWe performed fungal internal transcribed spacer 2 sequencing using fecal samples from 78 patients with NAFLD, 16 controls and 73 patients with alcohol use disorder. Anti-Candida albicans (C. albicans) IgG was measured in blood samples from 17 controls and 79 patients with NAFLD. Songbird, a novel multinominal regression tool, was used to investigate mycobiome changes. Germ-free mice were colonized with feces from patients with non-alcoholic steatohepatitis (NASH), fed a Western diet for 20 weeks and treated with the antifungal amphotericin B.ResultsThe presence of non-obese NASH or F2-F4 fibrosis was associated with a distinct fecal mycobiome signature. Changes were characterized by an increased log-ratio for Mucor sp./Saccharomyces cerevisiae (S. cerevisiae) in patients with NASH and F2-F4 fibrosis. The C. albicans/S. cerevisiae log-ratio was significantly higher in non-obese patients with NASH when compared with non-obese patients with NAFL or controls. We observed a different fecal mycobiome composition in patients with NAFLD and advanced fibrosis compared to those with alcohol use disorder and advanced fibrosis. Plasma anti-C. albicans IgG was increased in patients with NAFLD and advanced fibrosis. Gnotobiotic mice, colonized with human NASH feces and treated with amphotericin B were protected from Western diet-induced steatohepatitis.ConclusionsNon-obese patients with NAFLD and more advanced disease have a different fecal mycobiome composition to those with mild disease. Antifungal treatment ameliorates diet-induced steatohepatitis in mice. Intestinal fungi could be an attractive target to attenuate NASH.Lay summaryNon-alcoholic fatty liver disease is one of the most common chronic liver diseases and is associated with changes in the fecal bacterial microbiome. We show that patients with non-alcoholic fatty liver disease and more severe disease stages have a specific composition of fecal fungi and an increased systemic immune response to Candida albicans. In a fecal microbiome-humanized mouse model of Western diet-induced steatohepatitis, we show that treatment with antifungals reduces liver damage.

ObjectiveTo reduce children's sugar-sweetened beverage intake, California's Healthy-By-Default Beverage law (SB1192) mandates only unflavoured dairy/non-dairy milk or water be the default drinks with restaurant children's meals. The objective of this study is to examine consistency with this law for meals sold through online platforms from restaurants in low-income California neighbourhoods.DesignThis observational, cross-sectional study examines beverage availability, upcharges (additional cost) and presentation of beverage options consistent with SB1192 (using four increasingly restrictive criteria) within a random sample of quick-service restaurants (QSR) in Supplemental Nutrition Assistance Program Education eligible census tracts selling children's meals online from November 2020 to April 2021.SettingLow-income California neighbourhoods (n 226 census tracts).ParticipantsQSR that sold children's meals online via a restaurant-specific platform, DoorDash, GrubHub and/or UberEats (n 631 observations from 254 QSR).ResultsSeventy percent of observations offered water; 63 % offered unflavoured milk. Among all beverages, water was most likely to have an upcharge; among observations offering water (n 445), 41 % had an upcharge (average $0·51). Among observations offering unflavoured milk (n 396), 11 % had an upcharge (average $0·38). No observations upcharged for soda (regular or diet). Implementation consistency with SB1192 ranged from 40·5 % (using the least restrictive criteria) to 5·6 % (most restrictive) of observations.ConclusionsBased on observations from restaurant websites and three of the most popular online ordering platforms, most California QSR located in low-income neighbourhoods are not offering children's meal beverages consistent with the state's Healthy-By-Default Beverage law. As the popularity of online ordering increases, further work to ensure restaurants offering healthy default beverages with children's meals sold online is necessary.

Background and aimsNon-alcoholic fatty liver disease (NAFLD) is a global health burden. Risk factors for disease severity include older age, increased body mass index (BMI), diabetes, genetic variants, dietary factors and gut microbiota alterations. However, the interdependence of these factors and their individual impact on disease severity remain unknown.MethodsIn this cross-sectional study, we performed 16S gene sequencing using fecal samples, collected dietary intake, PNPLA3 gene variants and clinical and liver histology parameters in a well-described cohort of 180 NAFLD patients. Principal component analyses were used for dimensionality reduction of dietary and microbiota data. Simple and multiple stepwise ordinal regression analyses were performed.ResultsComplete data were available for 57 NAFLD patients. In the simple regression analysis, features associated with the metabolic syndrome had the highest importance regarding liver disease severity. In the multiple regression analysis, BMI was the most important factor associated with the fibrosis stage (OR per kg/m2 : 1.23, 95% CI 1.10-1.37, P

Background & aimsAlterations in the gut microbiome have been associated with the severity of nonalcoholic fatty liver disease (NAFLD). Previous studies focused exclusively on the bacteria in the microbiome; we investigated changes in the viral microbiome (virome) in patients with NAFLD.MethodsIn a prospective, cross-sectional, observational study, we extracted RNA and DNA virus-like particles from fecal samples from 73 patients with NAFLD: 29 patients had an NAFLD Activity Score (NAS) of 0-4, 44 patients had an NAS of 5-8 or liver cirrhosis (LCI), 37 patients had F0-F1 fibrosis, and 36 patients had F2-F4 fibrosis. As controls, 9 individuals without liver disease and 13 patients with mild primary biliary cholangitis were included in the analysis. We performed shotgun metagenomic sequencing of virus-like particles.ResultsPatients with NAFLD and NAS 5-8/LCI had a significant decrease in intestinal viral diversity compared with patients with NAFLD and NAS 0-4 or control individuals. The presence of more advanced NAFLD was associated with a significant reduction in the proportion of bacteriophages compared with other intestinal viruses. Using multivariate logistic regression analysis with leave-1-out cross validation, we developed a model, including a viral diversity index and simple clinical variables, that identified patients with NAS 5-8/LCI with an area under the curve of 0.95 (95% confidence interval, 0.91-0.99) and F2-F4 fibrosis with an area under the curve of 0.88 (95% confidence interval, 0.80-0.95). Addition of data on viral diversity significantly improved multivariate models, including those based on only clinical parameters or bacterial diversity.ConclusionsIn a study of fecal viromes from patients with NAFLD and control individuals, we associated histologic markers of NAFLD severity with significant decreases in viral diversity and proportion of bacteriophages. We developed a model based on fecal viral diversity and clinical data that identifies patients with severe NAFLD and fibrosis more accurately than models based only on clinical or bacterial data.

Many quick-service restaurants (QSRs) instituted voluntary kids' meal default beverage standards (standards) between 2013 to 2017. Little is known about impacts of standards on QSR drive-through practices and on customer choices. This study assessed differences in restaurant practices including kids' meal beverages shown on menu boards, offered by cashiers, and selected by customers in QSRs with and without voluntary standards. Observations (n = 111) and customer surveys (n = 84) were conducted in 2018 at QSRs with standards (n = 70) and without (n = 41) in low-income California, U.S. neighborhoods. Kids' meal beverages on menu boards (n = 149) and offered by cashiers (n = 185) at QSRs with and without standards were analyzed using multilevel logistic regression. Significantly more menu boards at QSRs with standards (n = 103) vs. without (n = 46) featured only milk, water or unsweetened juice (65.1% vs. 4.4%; p < 0.001). Most cashiers at QSRs with standards and QSRs without (53.1%, 62.5%) asked what drink the data collector wanted rather than first offering default beverages. A small sample of customer interviews found that customers at QSRs with standards most commonly ordered juice (37.0%); at QSRs without standards, soda (45.5%). Although menu boards showed healthier kids' meal beverages at QSRs with standards than without, cashier behavior was inconsistent. Results suggest additional measures (legislation, implementation support, enforcement) may be needed to ensure optimal implementation.

Social and occupational functioning deficits contribute to overall disability in hoarding disorder (HD), and psychiatric symptoms are likely strong contributors. In turn, social/occupational impairment and psychiatric illness are known to contribute to suicidality. However, few studies have examined the relationship between these factors. We examined these relationships in 313 treatment seeking individuals with HD, measuring hoarding severity with the Saving Inventory, Revised and functional impairment with the Activities of Daily Living for Hoarding Disorder (ADL-H). We created a composite social/occupational function variable assessing employment, cohabitation, and marriage. A path analysis was used to assess the relationship between social functioning, occupational functioning, hoarding related functional impairment in activities of daily living, hoarding severity, psychiatric burden, and suicidality in HD. At least one lifetime psychiatric comorbidity was noted in 61% of participants. High rates of unemployment, living alone, never marrying or being divorced/separated, and lifetime suicide attempts were present. Hoarding severity and hoarding-related functional impairment were associated with social/occupational impairment, and, along with psychiatric burden, with suicidality in this population. These findings suggest that thorough psychiatric evaluation and assessment of suicidality is warranted for those with HD, and that hoarding-related functional impairment is closely related to measures of real-world social functioning.

This study compares the effectiveness of approaches used to recruit a diverse sample for a randomized clinical trial for Hoarding Disorder (HD) in the San Francisco Bay Area. Of the 632 individuals who inquired about the study, 313 were randomized and 231 completed treatment. Most participants heard about the study via flyering (N = 161), followed by advocacy groups (N = 113), word of mouth (N = 84), health care professionals (N = 78), online (N = 68), and media (N = 11). However, those that heard about the study via advertising methods, such as flyers, were less likely to complete the study, p = .01, while those recruited via advocacy groups were most likely to be randomized, p = .03. No source proved more effective in recruiting underrepresented groups such as men, p = .60; non-whites, p = .49; or Hispanics, p = .97. Advertising recruited the youngest individuals, p