Association of the dietary index for gut microbiota and dietary inflammation index with metabolic dysfunction-associated steatotic liver disease and metabolic alcohol-associated liver disease

Abstract

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) and alcohol-associated metabolic dysfunction-associated liver disease (MetALD) are significant public health concerns, with diet playing a pivotal role in their pathogenesis. Aims: Using data from the National Health and Nutrition Examination Survey (NHANES) 2007-2018. This study investigates the associations of the dietary index for gut microbiota (DI-GM), dietary inflammatory index (DII), and their combined effects with MASLD/MetALD, while exploring the mediating roles of inflammation and metabolic dysfunction.

Methods: Data from the 2007 to 2018 NHANES included 9,529 participants. DI-GM and DII were calculated using 24-hour dietary recalls. Inflammatory and metabolic biomarkers-including triglyceride-glucose (TyG) index, metabolic score (MS), C-reactive protein (CRP), systemic immune inflammation index (SII), and systemic inflammatory response index (SIRI)-were analyzed. Multivariable logistic and linear regression, subgroup analyses, and restricted cubic spline (RCS) models assessed associations and dose-response relationships. Mediation analysis evaluated the roles of inflammatory and metabolic markers.

Results: Higher DI-GM scores were significantly associated with reduced MASLD (OR = 0.59, 95% CI: 0.46-0.75) and MetALD (OR = 0.57, 95% CI: 0.46-0.70). Conversely, higher DII scores were positively associated with MASLD (OR = 1.57, 95% CI: 1.23-2.01) and MetALD (OR = 1.40, 95% CI: 1.13-1.75). DI-GM was inversely associated with inflammation and metabolic markers (TyG: β= -0.05, MS: β= -0.11, CRP: β= -0.12, SII: β= -0.08, SIRI: β= -0.09), while DII exacerbated these markers (TyG: β= 0.06, MS: β= 0.18, CRP: β=0.14, SII: β= 0.11, SIRI: β= 0.10). The combined effects of DI-GM and DII further demonstrated that a gut microbiota-healthy and anti-inflammatory diet synergistically reduced MASLD (OR = 0.59, 95% CI: 0.43-0.81) and MetALD risks (OR = 0.58, 95% CI: 0.44-0.76). Mediation analysis confirmed that inflammation and metabolism significantly mediated the diet-disease associations (p < 0.05).

Conclusion: Higher DI-GM and lower DII are associated with reduced MASLD/MetALD risks, partially mediated by alleviating systemic inflammation and metabolic dysfunction. These findings highlight dietary interventions targeting gut microbiota and inflammation as strategies for early prevention of MASLD and MetALD.

Keywords: alcohol-associated metabolic dysfunction-associated liver disease; dietary index for gut microbiota; dietary inflammatory index; inflammation; metabolic dysfunction; metabolic dysfunction-associated steatotic liver disease.

Figure 1

Graphical abstract and flowchart of studied participants selection. NHANES, National Health and Nutrition Examination Survey; DI-GM, dietary index for gut microbiota; DII, dietary inflammation index; MASLD, metabolic dysfunction-associated steatotic liver disease; MetALD, metabolic dysfunction and alcohol-associated liver disease; Non-SLD, no steatotic liver disease; TyG, triglyceride-glucose index; MS, metabolic score; CRP, C-reactive protein; SII, systemic immune-inflammation index; SIRI, systemic inflammatory response index.

Figure 2

Association of DI-GM Tertiles, DII Tertiles and different combinations of DI-GM and DII with MASLD and MetALD, weighted. (A) DI-GM; (B) DII; (C) DI-GM&DII. DI-GM, dietary index for gut microbiota; DII, dietary inflammation index; MASLD, metabolic dysfunction-associated steatotic liver disease; MetALD, metabolic dysfunction and alcohol-associated liver disease; β, Standardized Coefficients; CI, Confidence interval. Crude model remained unadjusted; Model 1 adjusted for age, sex; Model 2 further adjusted for race/ethnicity, education level, marital status, PIR levels, diabetes, history of CVD, smoke, energy intake and physical activity. P for Trend: Tests for trends based on the variables containing the median values for each tertiles.

Figure 3

Association of DI-GM, DII with MASLD and MetALD using the RCS after adjustment for the covariables, weighted. (A) Association of DI-GM with MASLD. (B) Association of DII with MASLD. (C) Association of DI-GM with MetALD. DI-GM, dietary index for gut microbiota; DII, dietary inflammation index; MASLD, metabolic dysfunction-associated steatotic liver disease; MetALD, metabolic dysfunction and alcohol-associated liver disease; CI, Confidence interval.

Figure 4

Association of DI-GM Tertiles, DII Tertiles and different combinations of DI-GM and DII with TyG, MS, CRP, SII, SIRI in NHANES 2007–2018 participants, weighted. (A) DI-GM; (B) DII; (C) DI-GM&DII. DI-GM, dietary index for gut microbiota; DII, dietary inflammation index; MASLD, metabolic dysfunction-associated steatotic liver disease; MetALD, metabolic dysfunction and alcohol-associated liver disease; TyG, triglyceride- glucose index; MS, metabolic score; CRP, C-reactive protein; SII, systemic immune-inflammation index; SIRI, systemic inflammatory response index; OR: odd ratio; CI: Confidence interval. Crude model remained unadjusted; Model 1 adjusted for age, sex; Model 2 further adjusted for race/ethnicity, education level, marital status, PIR levels, diabetes, history of CVD, smoke, energy intake and physical activity; P for Trend: Tests for trends based on the variables containing the median values for each tertiles.

Figure 5

The mediated effects analysis of TyG, MS, CRP, SII, SIRI in the associations of DI-GM and DII with MASLD and MetALD. DI-GM, dietary index for gut microbiota; DII, dietary inflammation index; MASLD, metabolic dysfunction-associated steatotic liver disease; MetALD, metabolic dysfunction and alcohol-associated liver disease; TyG, triglyceride- glucose index; MS, metabolic score; CRP, C-reactive protein; SII, systemic immune-inflammation index; SIRI, systemic inflammatory response index; ACME, average causal mediation effects; ADE, average direct effects.