An integrated fecal microbiome and metabolome in the aged mice reveal anti-aging effects from the intestines and biochemical mechanism of FuFang zhenshu TiaoZhi(FTZ)

Background/Aims: Fufang Zhenzhu Tiao Zhi (FTZ) capsule is a Chinese herbal preparation under the guidance of professor Guo Jiao's new theory of "Tiaogan Qishu Huazhuo" for disorders of glucose and lipid metabolism for more than twenty yares, which has been demonstrated to exhibit potential anti-aging effects such as regulation of glucose and lipid metabolisms and antiinflammatory and antioxidative effects. This study attempts to reveal the anti-intestinal aging effect and possible mechanism of FTZ. Methods: The mice were divided into three groups: the control group, model group and treatment group. The treatment group was given 1.0 g/kg body weight of FTZ extract administered by oral gavage once a day for 12 consecutive weeks. Age-related alterations such as HE staining of intestinal tissue morphology, mRNA levels of intestinal telomerase and inflammatory cytokines were observed Fecal samples were used for ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOF/MS) and 16S rRNA gene sequencing analyses to reveal age-related metabolic perturbations and gut flora disorders to demonstrate the effects of FTZ. Results: Emerged pathological morphology of intestinal tissues, upregulated relative expression level of gut inflammatory factors and decreased relative expression level of telomerase mRNA in aging mice illustrated characteristic senescent phenotypes in model group. FTZ treatment significantly lowered intestinal inflammation levels, enhanced telomerase activity, partially reversed the fecal metabolites abnormalities and restored the disorders of intestinal flora. Multiple potential metabolites were associated with linoleic acid, glycerophospholipid, alpha-linolenic acid, biosynthesis of unsaturated fatty acids and glycerolipid metabolisms. Several decreased beneficial butyrate-producing bacteria like S24-7, possible Alkaliphilus belonging to the Clostridia class and increased harmful bacteria such as potentially toxic metabolite hydrogen sulfide-producer Bilophila and Desulfovibrio, inflammation-mediator Mucispirillum were determined in present aging mice. These age-related poor alterations could be partially attenuated by FTZ treatment. Conclusion: The pathologic changes of intestinal senescence and the decrease of telomerase mRNA in elderly mice was observed. FTZ may sever as a novel delaying intestinal aging strategy via three pathways for antiinflammatory, improving gut metabolites and gut flora. This study not only provided biological basis for the theory of treating different diseases with the same treatment in TCM, but also provided objective evidence for incorporating aging into the system of "glucose-lipid metabolism disease".