The regeneration of the mucosal interface of the human intestine is critical in the host–gut microbiome crosstalk associated with gastrointestinal diseases. The biopsy-derived intestinal organoids provide genetic information of patients with physiological cytodifferentiation. However, the enclosed lumen and static culture condition substantially limit the utility of patient-derived organoids for microbiome-associated disease modeling. Here, we report a patient-specific three-dimensional (3D) physiodynamic mucosal interface-on-a-chip (PMI Chip) that provides a microphysiological intestinal milieu under defined biomechanics. The real-time imaging and computational simulation of the PMI Chip verified the recapitulation of non-linear luminal and microvascular flow that simulates the hydrodynamics in a living human gut. The multiaxial deformations in a convoluted microchannel not only induced dynamic cell strains but also enhanced particle mixing in the lumen microchannel. Under this physiodynamic condition, an organoid-derived epithelium obtained from the patients diagnosed with Crohn’s disease, ulcerative colitis, or colorectal cancer independently formed 3D epithelial layers with disease-specific differentiations. Moreover, co-culture with the human fecal microbiome in an anoxic–oxic interface resulted in the formation of stochastic microcolonies without a loss of epithelial barrier function. We envision that the patient-specific PMI Chip that conveys genetic, epigenetic, and environmental factors of individual patients will potentially demonstrate the pathophysiological dynamics and complex host–microbiome crosstalk to target a patient-specific disease modeling.

Non-alcoholic fatty liver disease (NAFLD) is complicated disease and increasing worldwide. Previously, many studies of NALFD prevalences have used alanine aminotransferase (ALT) of > 40 U/L to define NAFLD, although that is too high to be reliable among adolescents. This study aimed to define the upper normal limit of ALT among Korean adolescents, and use it to estimate the prevalence of NAFLD, based on data from the Korea National Health and Nutrition Examination Survey (KNHANES). Data were obtained from 1785 healthy adolescents (916 boys and 869 girls, 10–18 years old) who participated in the KNHANES during 2010–2015. The International Diabetes Federation metabolic syndrome criteria for adolescents were used to exclude participants with metabolic syndrome components. Furthermore, participants who previously had diseases related to low HDL levels, high TG levels, diabetes, or very low/high body mass index and hepatitis B were excluded. The 95th percentiles level of ALT from healthy participants were evaluated. The definition of NAFLD was overweight status (≥85th percentile of body mass index) plus elevated ALT levels (95th percentile). The upper normal ALT were 24.1 U/L for boys and 17.7 U/L for girls. Based on these values, the estimated prevalences of NAFLD in 2015 were 8.9% among adolescents. Defining the upper normal limit of ALT can be adjusted for each sex and ethnics in the general population. ALT laboratory thresholds used for children should be re-examined. The physicians should be aware not to underdiagnose NAFLD patient even ALT level is < 40 U/L.

Kang Y, et al. J Korean Med Sci. 2018 Mar;33(14):e109. https://doi.org/10.3346/jkms.2018.33.e109

The prevalence and occurrence of mucin-degrading (MD) bacteria, such as Akkermansia muciniphila and Ruminococcus gnavus, is highly associated with human health and disease states. However, MD bacterial physiology and metabolism remain elusive. Here, we assessed functional modules of mucin catabolism, through a comprehensive bioinformatics-aided functional annotation, to identify 54 A. muciniphila genes and 296 R. gnavus genes. The reconstructed core metabolic pathways coincided with the growth kinetics and fermentation profiles of A. muciniphila and R. gnavus grown in the presence of mucin and its constituents. Genome-wide multi-omics analyses validated the nutrient-dependent fermentation profiles of the MD bacteria and identified their distinct mucolytic enzymes. The distinct metabolic features of the two MD bacteria induced differences in the metabolite receptor levels and inflammatory signals of the host immune cells. In addition, in vivo experiments and community-scale metabolic modeling demonstrated that different dietary intakes influenced the abundance of MD bacteria, their metabolic fluxes, and gut barrier integrity. Thus, this study provides insights into how diet-induced metabolic differences in MD bacteria determine their distinct physiological roles in the host immune response and the gut ecosystem.

Gi-Ung Kang, Sowon Park, Yeongyun Jung, Jai J. Jee, Min-Sueng Kim, Seungjun Lee, Dong-Woo Lee, Jae-Ho Shin, and Hong Koh. Gut and Liver 2022;16:775-85. https://doi.org/10.5009/gnl210369