Vitamin D Supplementation during Intensive Care Unit Stay Is Associated with Improved Outcomes in Critically Ill Patients with Sepsis: A Cohort Study.

BACKGROUND: Vitamin D, as a common micronutrient, has been widely used in critically ill patients. However, whether supplementation of vitamin D in adult patients with sepsis can improve their prognosis remains controversial. METHODS: Data from the Mart for Intensive Care IV database was used in this retrospective cohort study, and adult patients with sepsis were enrolled. Critically ill patients, admitted to intensive care units (ICUs) between 2008 and 2019 at the Beth Israel Deaconess Medical Center (BIDMC), were divided into the vitamin D supplementation group and non-vitamin D supplementation group. The primary outcomes were defined as all-cause in-hospital, 28-day, and 90-day mortality rates after admission to the ICU. A 1:1 propensity score matching (PSM), inverse probability of treatment weighting (IPTW), and overlap weighting (OW) analyses were used to minimize selection bias and balance the baseline demographic characteristics. Regression and survival analyses were performed to assess the association between vitamin D supplementation and clinical outcomes in patients with sepsis. RESULTS: In total, 3539 patients with sepsis were enrolled as study participants; of these, 315 were supplemented with vitamin D during their ICU stay. In-hospital, 28-day, and 90-day mortality rates were significantly lower in patients with sepsis supplemented with vitamin D. Multivariate regression analysis showed vitamin D supplementation as a potential protective factor for in-hospital mortality with an odds ratio (OR) = 0.70 (0.51-0.96) after adjusting for all confounders. The hazard ratios (HRs) for 28-day and 90-day mortality were 0.65 (0.50-0.85) and 0.70 (0.55-0.90), respectively. The survival analysis showed that the vitamin D supplementation group had a higher survival probability within 28 and 90 days (p-value < 0.05). These results remained relatively stable post PSM, IPTW, and OW. However, we found no evidence that vitamin D supplementation could shorten the length of stay in the ICU or hospital. CONCLUSIONS: Vitamin D supplementation during an ICU stay was associated with improved prognosis in patients with sepsis, as evidenced by lower in-hospital, 28-day, and 90-day mortality rates and lower disease severity-related scores, but showed no influence on the length of stay in the hospital or ICU.

Theabrownin from Pu-erh tea attenuates hypercholesterolemia via modulation of gut microbiota and bile acid metabolism.

Pu-erh tea displays cholesterol-lowering properties, but the underlying mechanism has not been elucidated. Theabrownin is one of the most active and abundant pigments in Pu-erh tea. Here, we show that theabrownin alters the gut microbiota in mice and humans, predominantly suppressing microbes associated with bile-salt hydrolase (BSH) activity. Theabrownin increases the levels of ileal conjugated bile acids (BAs) which, in turn, inhibit the intestinal FXR-FGF15 signaling pathway, resulting in increased hepatic production and fecal excretion of BAs, reduced hepatic cholesterol, and decreased lipogenesis. The inhibition of intestinal FXR-FGF15 signaling is accompanied by increased gene expression of enzymes in the alternative BA synthetic pathway, production of hepatic chenodeoxycholic acid, activation of hepatic FXR, and hepatic lipolysis. Our results shed light into the mechanisms behind the cholesterol- and lipid-lowering effects of Pu-erh tea, and suggest that decreased intestinal BSH microbes and/or decreased FXR-FGF15 signaling may be potential anti-hypercholesterolemia and anti-hyperlipidemia therapies.