Guangzhou University of Chinese Medicine

Ischemic heart disease (IHD) has remained the leading cause of death in the United States for over two decades, accounting for a large share of cardiovascular mortality. Thyroid disorders are known to worsen IHD progression, yet population-level evidence on their combined mortality burden is limited. This study leverages the CDC WONDER multiple-cause-of-death database to evaluate national trends and disparities in IHD mortality with coexisting thyroid disorders. We analyzed death certificate data from 1999 to 2023 for adults aged ≥ 25 years with IHD and thyroid disorders. Age-adjusted mortality rates (AAMRs) per 100,000 population were calculated. Temporal trends were assessed using Joinpoint regression, yielding annual percentage change (APC) and average annual percentage change (AAPC). From 1999 to 2023, 170,740 deaths were attributed to IHD with thyroid disorders. The overall AAMR declined from 7.35 in 1999 to 5.34 in 2023 (AAPC = - 1.40). Joinpoint regression showed a steady decline from 1999 to 2017 (APC = - 2.80), a temporary rise during 2017-2021 (APC = + 6.68), and a subsequent decrease from 2021 to 2023 (APC = - 4.18). Men consistently had higher AAMRs than women (13.23 vs. 10.03). Mortality was highest among non-Hispanic Black individuals, adults aged ≥ 85 years (56.95), and residents of rural areas (7.95 vs. 5.22 in urban areas). While overall mortality from IHD with thyroid disorders declined between 1999 and 2023, disparities by sex, race/ethnicity, age, and urban-rural status remain pronounced. These findings highlight the need for targeted prevention and intervention strategies to reduce inequities in this high-risk population. The online version contains supplementary material available at 10.1007/s40200-026-01931-6.

Type 2 diabetes mellitus (T2DM) is a global metabolic disorder where gut microbiota plays a causal therapeutic role. Bacteroides uniformis (B. uniformis, Bu) abundance inversely correlates with T2DM progression, but its mechanism remains unclear. This study employed T2DM rat models induced by high-fat feeding (HFD), low-dose streptozotocin (STZ), treated with Bu for six weeks. Methods included physiological monitoring, biochemical assays, histopathology, 16S rRNA gut microbiota sequencing, serum metabolomics, and in vitro HepG2 cell experiments under BCAA-deprived conditions to assess therapeutic mechanisms. Bu restored glucose-lipid homeostasis and reduced multi-organ oxidative/inflammatory damage in T2DM rats. 16S rRNA sequencing showed Bu reversed gut dysbiosis, restored microbial diversity, and enriched butyrate-producing bacteria, elevating fecal propionate and butyrate. Integration of non-targeted and targeted metabolomics further demonstrated that Bu specifically decreased circulating branched-chain amino acid (BCAA) levels, including leucine, isoleucine, valine, and their associated metabolites. In vitro validation confirmed that BCAA deprivation enhanced glucose uptake and attenuated lipid deposition in palmitate (PA)-induced insulin resistance (IR) in HepG2 cells. The present study demonstrates that Bu exerts multi-target modulation of the gut microbiota-metabolic axis, providing experimental evidence for its potential as a next-generation probiotic for T2DM prevention and treatment and associates the improvement with altered BCAA metabolism.