Maternal obesity is associated with increased risk for offspring obesity and non-alcoholic fatty liver disease (NAFLD), but the causal drivers of this association are unclear. Early colonization of the infant gut by microbes plays a critical role in establishing immunity and metabolic function. Here, we compare germ-free mice colonized with stool microbes (MB) from 2-week-old infants born to obese (Inf-ObMB) or normal-weight (Inf-NWMB) mothers. Inf-ObMB-colonized mice demonstrate increased hepatic gene expression for endoplasmic reticulum stress and innate immunity together with histological signs of periportal inflammation, a histological pattern more commonly reported in pediatric cases of NAFLD. Inf-ObMB mice show increased intestinal permeability, reduced macrophage phagocytosis, and dampened cytokine production suggestive of impaired macrophage function. Furthermore, exposure to a Western-style diet in Inf-ObMB mice promotes excess weight gain and accelerates NAFLD. Overall, these results provide functional evidence supporting a causative role of maternal obesity-associated infant dysbiosis in childhood obesity and NAFLD.

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In addition, the following was added to the Author contributions: 'B.Y. and N.F.K. helped to design the clinical study and participated in the sample collection during the infant visits.' This has been corrected in both the PDF and HTML versions of the Article.

Background: Several studies have explored hospitalization risk factors with the novel coronavirus disease 2019 (COVID-19) infection. Our goal was to identify clinical characteristics outside of laboratory or radiologic data associated with intubation or death within 7 days of admission. Methods: The first 436 patients admitted to the University of Colorado Hospital (Denver metropolitan area) with confirmed COVID-19 were included. Demographics, comorbidities, and select medications were collected by chart abstraction. Missing height for calculating body mass index (BMI) was imputed using the median height for patients’ sex and race/ethnicity. Adjusted odds ratios (aOR) were estimated using multivariable logistic regression and a minimax concave penalty (MCP) regularized logistic regression explored prediction. Results: Participants had a mean [standard deviation (SD)] age 55 (17), BMI 30.9 (8.2), 55% were male and 80% were ethnic/racial minorities. Increasing age [aOR: 1.24 (1.07, 1.45) per 10 years], higher BMI (aOR 1.03 (1.00, 1.06), and poorly controlled diabetes [hemoglobin A1C (HbA1c) ⩾ 8] (aOR 2.26 (1.24, 4.12) were significantly ( p < 0.05) associated with greater odds of intubation or death. Female sex [aOR: 0.63, 95% CI (0.40, 0.98); p value = 0.043] was associated with lesser odds of intubation or death. The odds of death and/or intubation increased 19% for every 1 unit increase in HbA1c value [OR: 1.19 (1.01, 1.43); p = 0.04]. Our final MCP model included indicators of A1C ⩾ 8, age > 65, sex, and minority status, but predicted intubation/death only slightly better than random chance [area under the receiver operating characteristic curve (AUC) = 0.61 (0.56, 0.67)]. Conclusion: In a hospitalized patient cohort with COVID-19, worsening control of diabetes as evidenced by higher HbA1c was associated with increased risk of intubation or death within 7 days of admission. These results complement and help clarify previous associations found between diabetes and acute disease in COVID-19. Importantly, our analysis is missing some known predictors of severity in COVID-19. Our predictive model had limited success, suggesting unmeasured factors contribute to disease severity differences.

Background While several studies have explored hospitalization risk factors with the novel coronavirus (COVID-19) infection, the risk of poor outcomes during hospitalization has primarily relied upon laboratory or hospital-acquired data. Our goal was to identify clinical characteristics associated with intubation or death within 7 days of admission. Methods The first 436 patients admitted to the University of Colorado Hospital (Denver metropolitan area) with confirmed CoVID-19 were included. Demographics, comorbidities, and select medications were collected by chart abstraction. Missing height for calculating body mass index (BMI) was imputed using the median height for patients’ sex and race/ethnicity. Adjusted odds ratios (aOR) were estimated using multivariable logistic regression and a minimax concave penalty (MCP) regularized logistic regression explored prediction. Results Participants had a mean(SD) age 55(17), BMI 30.9(8.2), 55% were male and 80% were ethnic/racial minorities. Unadjusted comparisons by outcome are shown (Table 1). Male sex (aOR: 1.60, 95% CI (1.02, 2.54)), increasing age (aOR: 1.25(1.08, 1.47); per 10 years), higher BMI (aOR 1.03(1.00, 1.06) and poorly controlled diabetes (hemoglobin A1C ≥8) (aOR 2.33(1.27, 4.27) were significantly (p&lt; 0.05) associated with greater odds of intubation or death. Minority status tended to be associated with higher odds (aOR:1.8(1.01,3.36); p=0.052). Surprisingly, need for hospital interpreter was associated with decreased odds (OR: 0.58(0.35, 0.95)) of intubation/death. Our final MCP model included indicators of A1C≥8, age &gt;65, sex and minority status, but predicted intubation/death only slightly better than random chance (AUC= 0.61(0.56, 0.67)). Table 1. Patient Characteristics Stratified by Intubation and/or Death Within One Week of Admission (n=436) Conclusion In a hospitalized patient cohort with COVID-19, male sex, poorly controlled diabetes, increasing age and BMI were significantly associated with early intubation or death. These results complement larger cohort studies, and highlight risk differences across metropolitan areas with varying COVID-19 prevalence, demographics, and comorbid disease burden. Notably, our predictive model had limited success, which may suggest unmeasured factors also contribute to disease severity differences. Disclosures All Authors: No reported disclosures