Food insecurity affects the health of college-aged individuals, but its impact on the gut microbiome (GM) over time is poorly understood. This study explored the association between food insecurity and the GM in eighty-five college students, identifying microbial taxa, metabolites and pathways linked to food security status and examining GM stability and microbe–metabolite interactions. Longitudinal GM and metabolomic data were collected from first-year students over an academic year, encompassing periods of variable food security status. Participants were categorised into three groups: food insecure (FI, n 13), food secure (FS, n 44) and variable (VAR, n 28) status. GM composition varied significantly between FS classifications (Bray–Curtis dissimilarity, P ≤ 0·005). Stability analysis revealed correlations between stability scores and microbial features, pathways and metabolites. Specific microbes (e.g. Bifidobacterium species, Faecalibacterium prausnitizii D and Lachnospiraceae), pathways (energy and microbial turnover) and metabolites (cadaverine, N-acetylcadaverine, putrescine, testosterone sulfate and creatine) associated with FI status were identified. Multi-omic integration revealed metabolic pathways influenced by differentially abundant microbial species and co-occurring fecal metabolites in FI participants related to the microbial production of polyamines, detoxification and energy metabolism. The transition from FS to FI showed no significant differences at specific taxonomic, functional or metabolite levels. This study uncovers complex interactions between food security, GM composition and metabolism. Significant differences were found in microbial community variability and metabolic pathways associated with food security status, but the transition from food security to insecurity disrupted the GM without clear taxonomic or functional distinctions, emphasising the need for further research into these mechanisms.