Objective To characterize the systemic effects of high-fat diet (HFD) -induced obesity across different ages, explore the microbiota-related obesity endotype using 16S rRNA sequencing, and identify key microbial genera as candidate markers for longitudinal monitoring and future interventional validation. Materials and methods Male C57BL/6J mice were randomly assigned to a standard chow diet (SCD) or HFD group, maintained until 4, 12 and 18 months of age as the young, middle-aged and old groups, respectively, at which time animals were euthanized. Systemic effects were evaluated by measuring body weight, Lee’s index, glucose-lipid metabolism, liver function, and blood oxygen levels, coupled with behavioral tests for mood and cognitive performance. Blood samples were collected to quantify LPS and Aβ1–42 levels using ELISA. Oral and fecal samples were collected for 16S rRNA sequencing to analyze microbiota diversity and community structure. Differential genera were identified by LEfSe, and those consistently altered in both oral and gut samples were operationally designated as marker genera. Targeted metabolomics was performed to analyze short-chain fatty acids (SCFAs). Correlations were evaluated using Spearman analysis. Results Compared with SCD, HFD mice showed systemic alterations across all age groups, including progressive obesity, elevated blood lipids and liver enzymes, accompanied by reduced blood oxygen, increased Aβ1–42 and LPS levels, increased anxiety-/depression-like behaviors, and impaired spatial memory. HFD significantly remodeled the alpha/beta-diversity and community structure of oral and gut microbiota, inducing stable enrichment of RomboutsiaB and depletion of beneficial genera (Bifidobacterium, Akkermansia, and Muribaculum). The abundance of RomboutsiaB positively correlated with obesity, blood lipids, liver enzyme levels, hypoxia, and inflammatory markers, but negatively correlated with multiple cognitive-behavioral parameters. Functional prediction and SCFA further profiling indicated that HFD enhanced lipid metabolism and environmental adaptation pathways, while reducing polysaccharide degradation and vitamin metabolism. Conclusions Long-term HFD is associated with systemic remodeling of the oral-gut-liver-brain axis across ages. RomboutsiaB, a pro-inflammatory–associated genus stably enriched in the oral and gut across all age groups, holds potential as a noninvasive microbial biomarker and candidate target for future intervention studies for obesity and its liver-brain comorbidities.
Tian et al. (Thu,) studied this question.