Background: As a newly proposed diagnosis, data on the prevalence of metabolic dysfunction-associated fatty liver disease (MAFLD) is rare. We aimed to assess the prevalence and risk factors of MAFLD using new definition in the contemporary South China population. Methods: In this population based, cross sectional study, a total of 5377 participants aged 30–79 years old were recruited from the South China between 2018 and 2019. MAFLD was diagnosed in subjects who have both hepatic steatosis and metabolic disorders according to the newly international expert consensus. The total prevalence of MAFLD and prevalence by sex and age was estimated. Demographic characteristics, history of disease, and lifestyle were recorded by participants on a questionnaire. Abdominal ultrasonography was performed and evaluated by experienced sonographers. Multivariable logistic regression was used to calculate the odds ratios (ORs) of MAFLD. Results: Overall prevalence of MAFLD was 29.2% (95% confidence interval [CI] 28.0% to 30.5%). Prevalence was higher in women (31.7%) than in men (25.5%; p < 0.001 for sex difference) and in subjects aged 50 years or older (30.7%) than in those aged 30–49 years (19.8%; p < 0.001 for age difference). In participants diagnosed with MAFLD, the prevalence of overweight/obesity was up to 90.5%, type 2 diabetes (T2DM) and metabolic dysregulation were 25.0% and 62.2%, respectively. Risk factors for MAFLD included overweight/obesity (OR = 4.67; 95% CI, 3.76–5.83), T2DM (OR = 2.41, 95% CI, 1.68–3.47), hypertriglyceridemia (OR = 2.42, 95% CI, 2.03–2.87), high school education (OR = 1.50, 95% CI, 1.23–1.82), high income (OR = 1.22, 95% CI, 1.05–1.42). A lower risk of MAFLD was associated with high physical activity equivalent (OR = 0.71, 95% CI, 0.60–0.85). A U-shaped association of frequency of soups and ORs of MAFLD was found, the adjusted ORs (95% CI) of lower and higher frequency of soups were 1.58 (1.32–1.89) and 1.36 (1.13–1.63), respectively. Conclusions: Our results showed a high prevalence of MAFLD in the general adult population in South China. Obesity has the greatest impact on MAFLD, physical activity and moderate consumption of soups might be the potential protective factors of MAFLD.

Epidemiological studies have demonstrated that high total protein intake was related to type 2 diabetes mellitus (T2DM) risks. However, few studies considered the impact of dietary pattern. We examined the associations between protein intake and T2DM in different dietary patterns. We used the demographic and dietary information of adults aged 18–75 years from the China Health and Nutrition Survey (2009), consisting of 4113 women and 4580 men. Dietary data was collected by using 24-h recalls combined with a food inventory for 3 consecutive days. Cluster analysis was used to classify subjects into groups, as determined by major sources of protein. Logistic regression models were used to calculate odds ratios (OR) and 95% confidence interval (95% CI) of T2DM according to the energy-adjusted protein intake. All participants were divided into three patterns according to the dietary source of protein (legumes and seafood, red meat, refined grains). Overall, plant protein intake was significantly and inversely associated with T2DM. In the subgroup analysis by dietary patterns, extreme quartile of plant protein intake was also inversely related to T2DM in the “legumes and seafood” group [OR = 0.58, 95% CI (0.33–0.96)]. Total protein intake and animal protein intake were positively related to T2DM in the “red meat” group [OR: 3.12 (1.65–5.91) and 3.48 (1.87–6.60), respectively]. However, the association of animal protein intake was reversed in the “refined grains” group [OR = 0.55, 95% CI 0.32–0.89]. The association between protein intake and T2DM varies by dietary pattern. Dietary pattern may be considered into the recommendation of protein intake for diabetes prevention.

Low-density lipoprotein (LDL) cholesterol (chol) subfractions are risk biomarkers for cardiovascular diseases (CVD). A reference analysis, ultracentrifugation (UC), is laborious and may be replaced with a rapid prediction using proton NMR spectra of human blood plasma. However, the quality and uniqueness of these prediction models of biologically related subfractions remains unknown. This study, using two independent cohorts (n = 277), investigates the inter-correlations between LDL cholesterol in the main fraction and five subfractions, as well as the independence of their NMR-based prediction models. The results reveal that the prediction models utilize both shared and unique spectral information from the NMR spectra to determine concentrations of LDL subfractions. Analysis of variance contributions for prediction and causality assessments demonstrate that the NMR spectra contain unique predictive information for the LDL1chol, LDL2chol, and LDL5chol subfractions. In contrast, the spectral signatures for LDL3chol and LDL4chol are either insufficient or confounded. Our findings indicate that these five CVD biomarkers represent two independent clusters, reflecting their biosynthetic pathways, and confirm the presence of causal relationships between certain LDL chol subfractions. This highlights the importance of employing caution when interpreting the concentrations of specific LDL subfractions as standalone biomarkers for CVD risk.

Background & aims: Human milk is the optimal diet for very preterm infants (VPIs), but it requires nutrient fortification to support growth. Bovine colostrum (BC), rich in intact proteins and bioactive components, could serve as a novel fortifier with potential benefits to VPIs gut health. To evaluate a possible effect of feeding BC on intestinal metabolism, the gut microbiota, and their interaction, we studied the fecal metabolome of VPIs in the first month of life, as compared with a conventional fortifier (CF, based on infant formula ingredients). Methods: Fecal samples were collected from VPIs recruited to the FortiColos trial (NCT03537365, BC, n = 107; CF, n = 112) before (FT0) and one (FT1) or two (FT2) weeks after start of fortification and analyzed using 1H NMR spectroscopy. Abundances of metabolites were compared between BC versus CF groups. Further, temporal changes in metabolite levels after start of fortification, as well as correlations with specific gut bacterial genera were explored. Results: Infants in the BC group had higher levels of fecal acetoacetate, choline, methanol, uracil, creatine, creatinine, lysine and a lower leucine at both FT1 and FT2, relative to the CF group. Asparagine, tryptophan and phenylalanine levels were higher, and butyrate was lower in the BC group at FT1. At FT2, higher fecal succinate and lower isoleucine were found in the BC group. In addition, eight metabolites (asparagine, phenylalanine, tryptophan, lysine, creatinine, acetoacetate, methanol and uracil) had fortification-specific changes over time. Positive correlations were found between succinate and unclassified Enterobacteriaceae, butyrate and Clostridium, uracil and Staphylococcus, while negative correlation were found between uracil and unclassified Enterobacteriaceae members. Conclusion: Our study shows distinct fecal metabolome profiles in VPIs in the first weeks after fortification with BC versus CF. The fortification- and time-specific gut metabolite changes suggest that fortifiers influence luminal nutrient metabolism and microbiota activity in VPIs. Fortifier type for human milk affected gut health of VPIs via altered gut metabolite levels, interacting with microbiota in VPIs. (c) 2024 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

Necrotising enterocolitis (NEC) is a microbiome-dependent gut disease in preterm infants in early life. Antibiotic treatment is a common intervention for NEC. How NEC lesions, with or without antibiotics, affect plasma metabolome was explored in this study. Formula-fed preterm pigs were used as a model for human NEC and treated with saline, parenteral or oral antibiotics (n = 15–17) for four days after delivery. Gut tissues were collected for evaluation of NEC-like lesions and plasma for metabolomic analysis by proton nuclear magnetic resonance spectroscopy (¹H-NMR). Metabolites were annotated, quantified and subjected to statistical modelling to delineate the effects of NEC and antibiotic treatment. Presence of severe NEC lesions, not antibiotic treatment, was the main drive for plasma metabolite changes. Relative to other pigs, pigs with severe NEC lesions had higher levels of alanine, histidine and myo-inositol, and lower levels of 3-hydroxybutyric acid and isobutyric acid. Across NEC lesion states (healthy, mild, severe), antibiotics directly affected only a few metabolites (tryptophan, 3-phenyllactic acid). Together and independently, NEC and antibiotic treatment affected circulating metabolites in preterm pigs. Amino acids and plasma metabolites, partly related to the gut microbiome, may be helpful to monitor progression of NEC lesions after proper validation.

Summary: Preterm infants are susceptible to neonatal sepsis, a syndrome of pro-inflammatory activity, organ damage and altered metabolism following infection. Given the unique metabolic challenges and poor glucose regulatory capacity of preterm infants, their glucose intake during infection may have a high impact on the degree metabolism dysregulation and organ damage. Using a preterm pig model of neonatal sepsis, we previously showed that a drastic restriction in glucose supply during infection protects against sepsis via suppression of glycolysis-induced inflammation, but results in severe hypoglycemia. Now we explored clinically relevant options of reducing glucose intake to decrease sepsis risk, without causing hypoglycemia and further explore the involvement of the liver in these protective effects. We found that a reduced glucose regime during infection increased survival via reduced pro-inflammatory response, while maintaining normoglycemia. Mechanistically, this intervention enhanced hepatic oxidative phosphorylation and possibly gluconeogenesis, and dampened both circulating and hepatic inflammation. However, switching from a high to a reduced glucose supply after debut of clinical symptoms did not prevent sepsis, suggesting metabolic conditions at the start of infection are key in driving the outcome. Finally, an early therapy with purified human inter-alpha inhibitor protein, a liver derived anti-inflammatory protein, partially reversed the effects of low parenteral glucose provision, likely by inhibiting neutrophil functions that mediate pathogen clearance. Our findings suggest a clinically relevant regime of reduced glucose supply for infected preterm infants could prevent or delay the development of sepsis in vulnerable neonates.