High-fructose intake is one of the high-risk factors for hypertension. Several probiotics have been reported to reduce high blood pressure (BP) via modulating gut microbiota, but the mechanism of the antihypertensive effect of probiotics is insufficiently understood. Herein, we investigated the antihypertensive effect of Bifidobacterium lactis M8 and Lactobacillus rhamnosus M9 based on the integrative analysis of gut metagenome and serum metabolome in high-fructose-treated mice. After 16-week intervention, M8 and M9 significantly reduced the median blood pressure by 16.92% and 15.39% in SBP, and 18.56% and 20.62% in DBP, respectively. Metagenomic analysis revealed that the increased Lawsonia and Pyrolobus , and reduced Alistipes and Alloprevotella levels were tightly correlated with lowered BP. Functionally, the decreased pathways of “base excision repair” (BER) and “D-glutamine and D-glutamate metabolism” were associated with BP reduction. Metabolomics data analysis further revealed that the probiotic interventions regulated vascular smooth muscle contraction, serotonergic synapse, cholinergic synapse, and lipid and vitamin metabolism in BP control. Additionally, association analyses indicated a strong negative correlation between Alistipes and “steroid hormone biosynthesis,” suggesting that Alistipes could affect blood pressure by changing steroid hormone levels. In conclusion, our findings indicate that the probiotic efficacies in alleviating hypertension are linked to specific gut microbes and metabolic pathways, which provide a potential mechanistic understanding of probiotics modulated blood pressure, paving the way for future assessment of the therapeutic potential of probiotics in hypertension management. IMPORTANCE: Elevated blood pressure affects 40% of the adult population, which accounts for high cardiovascular disease risk and further high mortality yearly. The global understanding of the gut microbiome for hypertension may provide important insights into the prevention. Bifidobacterium lactis M8 and Lactobacillus rhamnosus M9 originated from human breast milk, were able to decrease blood pressure, and modified metabolites in a high fructose-induced elevated blood pressure mouse model. Moreover, we found there was a close relationship between unexplored gut microbes and elevated blood pressure. Also, subsequently, the cross-link was explored among gut microbes, metabolites, and some metabolic pathways in gut microbial environment through introducing novel prediction methodology and bioinformatic analysis. It allowed us to hypothesize that probiotics can prevent elevated blood pressure via gut microbiota and related metabolism.Thus, utilization of dietary strategies (such as probiotics) to maintain the blood pressure level is of crucial importance.

Gut microbiome may influence tumor growth and cancer treatment efficacy, so it is a potential target for tumor prevention/treatment. This pilot study investigated the preventive and therapeutic effects of a probiotic strain, Lacticaseibacillus rhamnosus Probio-M9 (Probio-M9), against murine mammary cancer. Thirty-six female mice were randomly divided into three groups (n = 12 per group): control (without tumor transplantation), model (tumor transplantation; no probiotic administration), and probiotic (30-day oral gavage of probiotic, started seven days before tumor transplantation). Changes in tumor size were recorded, and blood, tumor tissue, and stool samples were collected at the end of the trial for analyses. Comparing with the model group, the probiotic group had a significantly smaller tumor volume (p < 0.05), a higher fecal microbiota Shannon diversity index, with significant modifications in the gut microbiota structure (p < 0.05), characterized by more Alistipes sp._2, Porphyromonadaceae bacterium_7, and Bacteroidales bacterium 55_9 (p < 0.05). Additionally, Probio-M9 administration elevated the serum IFN-γ, IL-9, IL-13, and IL-27 levels and several metabolites (e.g., pyridoxal, nicotinic acid, 3-hydroxybutyric acid, glutamine; p < 0.05), while reducing IL-5 (p < 0.05). These changes might be associated with the protective effect of Probio-M9 against mammary tumor growth. Thus, probiotic administration could harness host gut microbiome in anti-cancer responses.

Colorectal cancer (CRC) is the third highest cause of cancer-related death and the main option for prolonged survival is chemotherapeutic intervention. There is increasing interest in dietary intervention using natural agents to enhance the sensitivity of such invasive chemical treatment. In this study, the chemotherapeutic efficacy of dihydromyricetin (DMY) intervention on treatments involving irinotecan (CPT-11) or gemcitabine (GM) was evaluated in an AOM/DSS-induced colitis-associated colon cancer model and a Min (Apc Min/+) mice model. Our data showed that DMY could promote the CPT-11 effect both in the mouse model of AOM/DSS and Apc Min/+ cancer and had no influence on the GM effect. In AOM/DSS cancer, tumors were sensitive to 100 mg kg⁻¹ DMY chemotherapy under 100 mg kg⁻¹ or 200 mg kg⁻¹ CPT-11. DMY-driven CPT-11 chemotherapy induced enhanced IgG levels and the reduction of Fusobacterium abundance in the gut. In the Min model, CPT-11 with 20 mg kg⁻¹ DMY prevented tumor formation but not with 100 mg kg⁻¹ DMY. Mechanically, chloride ion-dependent CFTR, CLCN4, and CLIC4 signaling are not involved in DMY mediated chemotherapeutic colon tumorigenesis. These results suggested that a suitable dose of DMY could act as a coadjuvant to CPT-11 chemotherapy.

This study aimed to evaluate the functional and probiotic properties of Lactobacillus acidophilus SJLH001 (La-SJLH001) isolated from fermented food via mechanism analysis based on transcriptomics and culturomics. La-SJLH001 exhibited good tolerance to acid and bile salt conditions with anti-diabetic ability and cholesterol assimilation activity in vitro. Supplementation with La-SJLH001 also resulted in a significant reduction in host oral glucose and serum total cholesterol levels in vivo. Transcriptome profiles and qPCR analysis suggested that La-SJLH001 significantly regulated the transcription of key genes involved in glucose transportation, cholesterol metabolism, ion channels, and immune response, resulting in improved glucose homeostasis and cholesterol metabolism. La-SJLH001 significantly affected the structure of intestinal microbiota when analyzed by using culturomics coupled with MALDI-TOF MS. These results indicated that La-SJLH001 may be a mechanistic target for the control of diabetes with great potential in the application of probiotic products.