(OR24-02-26) Sex-Specific Differences in Gut Microbial Alpha Diversity Following Six Weeks of Almond vs Cookie Snacking in Adults With Obesity

Objectives: To determine whether daily almond consumption alters gut microbial alpha diversity compared with an isocaloric cookie snack over six weeks and whether responses differ by sex in adults with obesity.

Methods: Participants (BMI: 30–45 kg/m²; age 30–45 years; N = 69) were randomized to consume 57 g/day whole almonds (n = 38) or an isocaloric cookie snack (66 g/day; n = 31) for 6 weeks in a parallel-arm randomized controlled trial. Stool samples were collected at baseline and week 6 for microbiome analysis. Deep shotgun metagenomic sequencing (40-79 million reads per sample) was used to characterize the gut microbiome. Raw reads underwent quality control using FastQC followed by trimming and host read removal prior to taxonomic profiling with MetaPhlAn v4. Alpha diversity metrics, including the Shannon and Simpson diversity indices, and overall richness, were calculated across taxonomic classification levels. Baseline-adjusted linear models were used to evaluate Group × Sex effects at week 6. Post hoc comparisons were conducted for significant interaction effects with adjustment for multiple testing using multivariate t adjustment, and effect sizes were calculated using Cohen’s d.

Results: Baseline-adjusted analyses at week 6 revealed significant Group × Sex interaction effects for Shannon and Simpson indices at the class and order taxonomic levels (baseline-adjusted p < 0.05). Post hoc comparisons for interaction effects indicated that within the almond group, females exhibited higher Shannon indices at the class and order levels and higher Simpson indices at the class level than males (d = 1.20–1.22, baseline-adjusted p < 0.05). No sex differences were observed in the cookie group. A main effect of group was also observed for phylum-level richness, with higher richness in the almond group than the cookie group at week 6 (d = 0.67, baseline-adjusted p < 0.05).

Conclusions: Sex may influence how the gut microbiome responds to specific dietary interventions, and our findings suggest that almonds may promote a more diverse and evenly distributed gut microbial community in females than in males. Future analyses should focus on the specific taxa driving these differences, the functional capacity of the microbiome, and how they associate with health in obesity.

Funding Sources: Almond Board of California