Lean Mass Gain from a Moringa-Enriched Protein Diet Confers Reno-Protective Effects and Modulates Gut Microbiota and sACE2 Activity

Obesity and protein-energy malnutrition represent dual nutritional challenges, with high-protein diets often prescribed to restore lean mass but simultaneously risking renal overload. Moringa oleifera (MOL), a nutrient-rich plant with antioxidant and prebiotic properties, may offer a dietary strategy to improve muscle metabolism, microbial balance, and renal protection, particularly when combined with exercise.This study evaluated the effects of 2% and 4% MOL in 20% protein diet and 8% MOL in 40% protein diet, with or without forced swimming, and study includes three experimental phases in NIN/Sprague Dawley, Wistar/NIN, and obese mutant rats ( Ob/ob and Gr/ob ). In Phase I (20% protein diet), MOL improved neuromuscular performance: grip strength increased by 21–26% compared with 7.6% in controls (p < 0.0001). Gastrocnemius glycogen decreased by 15–35% (p < 0.0001), reflecting greater glycogen utilization. Morphometry revealed fiber hypertrophy, with short fibers enlarging by 87% in Group 5 (p < 0.0001) in gastrocnemius muscles. Phase II demonstrated microbiota remodeling, with Lactobacillus and Bifidobacteria increasing by 08–26% and the Firmicutes/Bacteroides ratio decreasing by up to 11%. Circulating sACE2 declined by 7–52% with MOL, contrasting with elevations in Ob/ob rats (+ 64%). Phase III, involving 40% protein diets, revealed renal stress with elevated NAGase (~ 45 ng/mL) and β2-microglobulin (+ 11%); these were attenuated by MOL with fiber (− 49%).Collectively, MOL enhanced muscle performance, promoted microbial homeostasis, lowered sACE2, and provided renoprotection under high-protein load, particularly when combined with exercise. These findings highlight MOL as a functional food candidate for obesity management and metabolic resilience.