Late-in-life treadmill training mitigates gut microbiome imbalances and cardiovascular disease risk in mice

American Journal of Physiology-Gastrointestinal and Liver Physiology · 2026-02-03

It is unknown whether exercise training, if started late-in-life, reestablishes a beneficial and cooperative intestinal microbiome. Here we demonstrate that a 12-wk treadmill running program in older mice rejuvenates the gut microbiome and attenuates markers of cardiovascular disease (CVD) risk. Notably, specific microbial taxa correlate with activity-induced improvements in overall myocardial performance and inflammation, highlighting the importance of gut health on CVD and illustrating the restorative benefits that can be attained from a low-cost lifestyle intervention.

Supplemental Figure 4 from Metabolic Phenotype and Risk of Obesity-Related Cancers in the Women’s Health Initiative

2025-02-03

<p>Supplemental Figure 4. Hazard ratios and 95% confidence intervals for the association of metabolic phenotype defined by the Wildman criteria with obesity-related cancer risk, stratified by cancer type among postmenopausal women in the Women’s Health Initiative. Model adjusted for demographics (age, education, race/ethnicity, marital status), lifestyle (smoking status, physical activity, alcohol use, fruits and vegetable intake, fiber intake, read meat intake), hormonal factors for female cancers (parity, hormone therapy use), family history of ORC and study ID. MUNW=metabolically unhealthy normal weight; MHO=metabolically healthy overweight/obese; MUO= metabolically unhealthy overweight/obese. Metabolically healthy normal weight (MHNW) is the comparison group.</p>

Supplemental Table 7 from New-Onset Diabetes after an Obesity-Related Cancer Diagnosis and Survival Outcomes in the Women's Health Initiative

2025-11-26

<p>Supplemental Table 7 provides results for the 6 months lag analysis.</p>

Supplemental Table 1 from New-Onset Diabetes after an Obesity-Related Cancer Diagnosis and Survival Outcomes in the Women's Health Initiative

2025-11-26

<p>Supplemental Table 1 provides demographic characteristics for the included and excluded participants in the study.</p>

Supplemental Table 3 from New-Onset Diabetes after an Obesity-Related Cancer Diagnosis and Survival Outcomes in the Women's Health Initiative

2025-11-26

<p>Supplemental Table 3 provides effect estimates for the association of incident diabetes and all-cause mortality among obesity-related cancer survivors and cancer-free individuals, stratified by covariates that did not meet PH assumptions.</p>

Supplemental Table 7 from Metabolic Phenotype and Risk of Obesity-Related Cancers in the Women’s Health Initiative

2025-02-03

<p>Supplemental Table 7. Association between metabolic phenotypes defined by Wildman criteria with obesity-related cancer (ORC) risk after excluding participants diagnosed with ORC within the first three years of follow-up in the Women’s Health Initiative cohort (N= 20,320).</p>

Data from Metabolic Phenotype and Risk of Obesity-Related Cancers in the Women’s Health Initiative

2025-02-03

<div>Abstract<p>Body mass index (BMI) may misclassify obesity-related cancer (ORC) risk, as metabolic dysfunction can occur across BMI levels. We hypothesized that metabolic dysfunction at any BMI increases ORC risk compared with normal BMI without metabolic dysfunction. Postmenopausal women (<i>n</i> = 20,593) in the Women’s Health Initiative with baseline metabolic dysfunction biomarkers [blood pressure, fasting triglycerides, high-density lipoprotein cholesterol, fasting glucose, homeostatic model assessment for insulin resistance (HOMA-IR), and high-sensitive C-reactive protein (hs-CRP)] were included. Metabolic phenotype (metabolically healthy normal weight, metabolically unhealthy normal weight, metabolically healthy overweight/obese, and metabolically unhealthy overweight/obese) was classified using four definitions of metabolic dysfunction: (i) Wildman criteria, (ii) National Cholesterol Education Program Adult Treatment Panel III, (iii) HOMA-IR, and (iv) hs-CRP. Multivariable Cox proportional hazards regression, with death as a competing risk, was used to assess the association between metabolic phenotype and ORC risk. After a median (IQR) follow-up duration of 21 (IQR, 15–22) years, 2,367 women developed an ORC. The risk of any ORC was elevated among metabolically unhealthy normal weight (HR = 1.12, 95% CI, 0.90–1.39), metabolically healthy overweight/obese (HR = 1.15, 95% CI, 1.00–1.32), and metabolically unhealthy overweight/obese (HR = 1.35, 95% CI, 1.18–1.54) individuals compared with metabolically healthy normal weight individuals using Wildman criteria. The results were similar using Adult Treatment Panel III criteria, hs-CRP alone, or HOMA-IR alone to define metabolic phenotype. Individuals with overweight or obesity with or without metabolic dysfunction were at higher risk of ORCs compared with metabolically healthy normal weight individuals. The magnitude of risk was greater among those with metabolic dysfunction, although the CIs of each category overlapped.</p><p><b>Prevention Relevance:</b> Recognizing metabolic dysfunction as a significant risk factor for ORCs underscores the importance of preventive measures targeting metabolic health improvement across all BMI categories.</p></div>

Dietary Prebiotics Modulate Omeprazole‐Induced Alterations in the Gut Microbial Signature

Molecular Nutrition & Food Research · 2025-10-30

Proton pump inhibitors (PPIs) are commonly used to treat heartburn and acid-related disorders. However, their misuse and prolonged use contribute to gut dysbiosis. This study investigated whether well-known prebiotic dietary sources, blueberries or strawberries, can reverse PPI (omeprazole) induced dysbiosis and gut inflammation by modulating gut microbes. Male C57BL/6J mice (7 weeks old) were fed a diet with or without omeprazole (40 mg/kg diet), blueberry (3.7% in the diet; ∼1.5 human servings) or strawberry (2.35% in the diet; ∼2 human servings) for 12 weeks. Metabolic parameters, gut microbes (in the cecum and colon), and inflammatory markers were assessed. In this study, no changes were observed in metabolic parameters in mice fed a diet supplemented with omeprazole or berries. Second, blueberry or strawberry supplementation at nutritional dosages improved alterations in gut microbial ecology induced by omeprazole, with effects varying between the cecum and colon. Third, strawberry supplementation reduced omeprazole-induced gut inflammation. Fourth, selected genera were either positively or negatively associated with markers of gut inflammation, suggesting that dietary berries can ameliorate inflammatory signaling through modifications in the gut microbiome. Dietary berries represent a potential nutritional strategy for improving PPI-induced gut dysbiosis and inflammation.

Supplemental Table 6 from Metabolic Phenotype and Risk of Obesity-Related Cancers in the Women’s Health Initiative

2025-02-03

<p>Supplemental Table 6. Association between metabolic phenotypes defined by Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) with obesity-related cancer risk in the Women’s Health Initiative cohort (N= 23,232).</p>

Supplemental Table 2 from Metabolic Phenotype and Risk of Obesity-Related Cancers in the Women’s Health Initiative

2025-02-03

<p>Supplemental Table 2. Association between metabolic phenotypes defined by Wildman criteria with obesity-related cancer risk in the Women’s Health Initiative cohort (N= 20,593).</p>