Daily Endocrinology Research Analysis

Metabolic dysfunction-associated steatotic liver disease (MASLD) is increasingly linked to gut microbial dysbiosis, but most studies have focused on bacteria, neglecting viruses and fungi, and their interactions. Here we show that MASLD is characterized by coordinated disruption of bacterial, viral and fungal communities and by a disturbed phage-bacteria-metabolite axis associated with disease-related bile acid changes. Integrating shotgun metagenomics, fungal ITS2 sequencing, fecal metabolomics and clinical profiling in 210 patients with MASLD and 210 age- and gender-matched healthy controls, we find reduced microbial diversity and extensive remodeling of cross-kingdom ecological networks in MASLD. Ruminococcus gnavus emerges as an enriched central hub, while Faecalibacterium prausnitzii and its associated bacteriophages are depleted. Phage-host analyses further reveal reduced lytic activity against R. gnavus and loss of sulfur amino acid metabolism-related auxiliary metabolic genes, which may impair F. prausnitzii fitness. Diminished phage control may facilitate R. gnavus expansion, alongside increased fecal isodeoxycholic acid, a secondary bile acid implicated in hepatic steatosis. A diagnostic classifier integrating bacterial and viral features with clinical parameters distinguish MASLD from controls in our cohort and maintain predictive performance in two external datasets. Together, these findings uncover a disrupted phage-bacteria-metabolite axis in MASLD and provide a multi-kingdom framework for non-invasive biomarker discovery and microbiome-targeted therapies.

Metabolic dysfunction-associated fatty liver disease (MAFLD) is increasingly common among candidates for metabolic and bariatric surgery, yet clinical thresholds defining when surgery is beneficial or contraindicated remain unclear. This systematic review and meta-analysis synthesized evidence from 29 studies including 71,904 patients with biopsy-confirmed or elastography-confirmed MAFLD undergoing sleeve gastrectomy, Roux-en-Y gastric bypass, or other metabolic procedures. Bariatric surgery was associated with marked hepatic and endocrine improvement, with pooled remission rates of 70% for steatohepatitis, 57% for fibrosis, and 59% for type 2 diabetes. Both sleeve gastrectomy and Roux-en-Y gastric bypass achieved comparable metabolic and hepatic benefits, supporting the role of weight-independent mechanisms such as enhanced incretin signaling and improved insulin sensitivity. Postoperative complications occurred in 15% of patients, including 4% major complications, indicating an overall acceptable safety profile. Across studies, patients with compensated cirrhosis experienced meaningful hepatic improvement, whereas those with decompensated cirrhosis, clinically significant portal hypertension, or impaired hepatic reserve had higher morbidity and limited benefit. Endocrine instability-particularly poorly controlled endocrine disease (e.g., uncontrolled diabetes or untreated thyroid dysfunction)-also emerged as a relative contraindication due to impaired healing and unpredictable metabolic responses. These findings underscore the need for careful preoperative evaluation integrating liver staging, endocrine profiling, and metabolic capacity. Overall, bariatric surgery provides substantial hepatic and endocrine benefits for appropriately selected MAFLD patients, while advanced cirrhosis and uncontrolled endocrine disease represent key thresholds at which surgical risk may outweigh benefit. A multidisciplinary liver-endocrine approach is essential for optimal candidate selection and postoperative outcomes.

BACKGROUND AND AIM: The normalized creatinine-to-cystatin C ratio (NCCR) has recently emerged as a contributor to diabetes risk. However, its association with hypertension remains elusive. This study aimed to investigate this relationship in a large-scale prospective cohort. METHODS AND RESULTS: Based on the China Health and Retirement Longitudinal Study (CHARLS), a total of 4794 participants aged ≥45 years were enrolled from five CHARLS surveys in 2011, 2013, 2015, 2018 and 2020. Logistic regression models were used to investigate the association between NCCR and hypertension. The joint effects of body mass index and NCCR on the risk of hypertension were further analyzed. Additionally, the C-statistic was used to assess the predictive performance of NCCR for hypertension risk. During follow-up, 1318 (27.49 %) participants developed hypertension. After full adjustment for confounders, each per-SD increment in NCCR was associated with a significantly lower risk of hypertension (odds ratio [OR] = 0.81, 95% CI: 0.76 - 0.88, P < 0.001). Sex- and age-specific analyses revealed that the significant inverse associations between NCCR and hypertension were more pronounced in females and middle-aged individuals. Notably, non-obese participants with high NCCR experienced a more significant risk reduction than those who were obese with high NCCR. Moreover, incorporating NCCR into the basic model significantly improved the predictive ability for hypertension. CONCLUSIONS: Higher levels of NCCR were independently associated with a decreased risk of hypertension in middle-aged and older adults, especially in females and middle-aged individuals.