SUN-721 - Metabolic and Microbiome Responses to Very Low-Calorie Diet in Women with Obesity and Metabolic Dysfunction-Associated Steatotic Liver Disease

Background: Weight loss is the cornerstone treatment for metabolic dysfunction-associated steatotic liver disease (MASLD). Nevertheless, the effect of weight loss on the microbiome remain incompletely defined in the setting of MASLD. We evaluated oral and fecal microbiome responses to very low-calorie diet (VLCD)-induced weight loss in women with obesity and MASLD.

Methods: In this prospective, non-parallel intervention study, 10 women with obesity and MASLD [median age 42 years (IQR 37-46); controlled attenuation parameter (CAP) ≥248 dB/m] consumed an 800 kcal/day VLCD for 8 weeks. Anthropometric, metabolic, and hepatic measures were assessed pre- and post-intervention. Hepatic steatosis and stiffness were quantified by transient elastography. Subgingival plaque, saliva, and stool samples were collected before and after weight loss. Microbial DNA was extracted and V3-V4 regions sequenced (Illumina MiSeq 2×300 bp). Oral and fecal microbiomes were annotated using the Human Oral Microbiome and Greengenes Databases, respectively. Longitudinal analyses were performed using timeOmics, with each participant serving as her own control.

Results: Adherence to VLCD was 79% (71–88%). Mean weight decreased by 12.7 ± 1.1 kg (11% from baseline; p< 0.0001), with significant reductions in waist (−9.3 ± 1.5 cm) and neck circumference (−2.1 ± 0.2 cm). Body fat percentage per bioimpedance declined by 2.0 ± 0.5% (p=0.0006). Systolic and diastolic blood pressures decreased by 12.7 ± 3.6 mmHg and 9.0 ± 1.6 mmHg, respectively. HbA1c (−0.32 ± 0.07%), HOMA-IR (−1.95 ± 0.69), and triglycerides (−36.6 ± 11.6 mg/dL) improved significantly, while fasting glucose and liver enzymes remained unchanged. CAP decreased by 106.1 ± 16.3 dB/m (p=0.0001), indicating marked reduction in hepatic steatosis. Liver stiffness did not change. Across oral and gut niches, post-diet samples demonstrated reduced alpha diversity and distinct niche-specific microbial remodeling. Weight loss was associated with enrichment of health-associated taxa (Neisseria, Veillonella, Rothia) and reduction of disease-associated species (Prevotella, Tannerella spp.).

Conclusion: VLCD-induced weight loss was associated with reductions in hepatic steatosis, insulin resistance, and cardiometabolic risk in women with obesity and MASLD. Importantly, weight loss was accompanied by niche-specific shifts in oral and fecal microbiomes toward health-associated profiles. These findings suggest that dietary weight loss may concurrently modulate metabolic and microbial pathways relevant to MASLD pathophysiology.

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