Dairy products—encompassing yogurt, kefir, cheese, and cultured milk beverages—are emerging as versatile, food-based modulators of gut microbiota and host physiology. This review synthesizes mechanistic insights demonstrating how live starter cultures and their fermentation-derived metabolites (short-chain fatty acids, bioactive peptides, and exopolysaccharides) act synergistically to enhance microbial diversity, reinforce epithelial barrier integrity via upregulation of tight-junction proteins, and modulate immune signaling. Clinical evidence supports significant improvements in metabolic parameters (fasting glucose, lipid profiles, blood pressure) and reductions in systemic inflammation across metabolic syndrome, hypertension, and IBS cohorts. We highlight critical modulatory factors—including strain specificity, host enterotypes and FUT2 genotype, fermentation parameters, and matrix composition—that govern probiotic engraftment, postbiotic yield, and therapeutic efficacy. Despite promising short-term outcomes, current studies are limited by heterogeneous designs and brief intervention periods, underscoring the need for long-term, adaptive trials and integrative multi-omics to establish durability and causality. Looking forward, precision nutrition frameworks that harness baseline microbiota profiling, host genetics, and data-driven fermentation design will enable bespoke fermented dairy formulations, transforming these traditional foods into next-generation functional matrices for targeted prevention and management of metabolic, inflammatory, and neuroimmune disorders.

In our previous research, Lactiplantibacillus plantarum-12 alleviated inflammation in dextran sodium sulfate (DSS)-induced mice by regulating intestinal microbiota and preventing colon shortening (p < 0.05). The purpose of the present study was to evaluate whether L. plantarum-12 could ameliorate the colon cancer symptoms of azoxymethane (AOM)/DSS-treated C57BL/6 mice. The results showed that L. plantarum-12 alleviated colonic shortening (from 7.43 ± 0.15 to 8.23 ± 0.25) and weight loss (from 25.92 ± 0.21 to 27.75 ± 0.88) in AOM/DSS-treated mice. L. plantarum-12 oral administration down-regulated pro-inflammatory factors TNF-α (from 350.41 ± 15.80 to 247.72 ± 21.91), IL-8 (from 322.19 ± 11.83 to 226.08 ± 22.06), and IL-1β (111.43 ± 8.14 to 56.90 ± 2.70) levels and up-regulated anti-inflammatory factor IL-10 (from 126.08 ± 24.92 to 275.89 ± 21.87) level of AOM/DSS-treated mice. L. plantarum-12 oral administration restored the intestinal microbiota dysbiosis of the AOM/DSS treated mice by up-regulating beneficial Muribaculaceae, Lactobacillaceae, and Bifidobacteriaceae levels and down-regulating pathogenic Proteobacteria, Desulfovibrionaceae, and Erysipelotrichaceae levels. As a result, the fecal metabolites of the AOM/DSS-treated mice were altered, including xanthosine, uridine, 3,4-methylenesebacic acid, 3-hydroxytetradecanedioic acid, 4-hydroxyhexanoylglycine, beta-leucine, and glycitein, by L. plantarum-12 oral administration. Furthermore, L. plantarum-12 oral administration significantly ameliorated the colon injury of the AOM/DSS-treated mice by enhancing colonic tight junction protein level and promoting tumor cells death via down-regulating PCNA (proliferating cell nuclear antigen) and up-regulating pro-apoptotic Bax. (p < 0.05). Taken together, L. plantarum-12 oral administration could ameliorate the colon cancer burden and inflammation of AOM-DSS-treated C57BL/6 mice through regulating the intestinal microbiota, manipulating fecal metabolites, enhancing colon barrier function, and inhibiting NF-κB signaling. These results suggest that L. plantarum-12 might be an excellent probiotic candidate for the prevention of colon cancer.

Exopolysaccharide produced by Lactiplantibacillus plantarum-12 (LPEPS) exhibited the anti-proliferating effect on human colon cancer cell line HT-29 in vitro. The purpose of the study was to determine the alleviating effects of LPEPS on colon cancer development of the C57BL/6 mice treated by azoxymethane/dextran sulfate sodium salt (AOM/DSS). The C57BL/6 mice treated by AOM/DSS were orally administered LPEPS daily for 85 days. The results showed that LPEPS oral administration enhanced colon tight-junction protein expression and ameliorated colon shortening and tumor burden of the AOM/DSS treated mice. Furthermore, LPEPS oral administration significantly reduced pro-inflammatory factors TNF-α, IL-8, and IL-1β levels and increased anti-inflammatory factor IL-10 level in the serum of the AOM/DSS-treated mice. LPEPS oral administration reversed the alterations of gut flora in AOM/DSS-treated mice, as evidenced by the increasing of the abundance of Bacteroidetes, Bacteroidetes/Firmicutes ratio, Muribaculaceae, Burkholderiaceae, and norank_o__Rhodospirillales and the decreasing of the abundance of Firmicutes, Desulfovibrionaceae, Erysipelotrichaceae, and Helicobacteraceae. The fecal metabolites of the AOM/DSS-treated mice were altered by LPEPS oral administration, involving lipid metabolism and amino acid metabolism. Together, these results suggested that LPEPS oral administration alleviated AOM/DSS-induced colon cancer symptoms of the C57BL/6 mice by modulating gut microbiota and metabolites, enhancing intestine barrier, inhibiting NF-κB pathway, and activating caspase cascade.

This study aims to elucidate the mechanism by which exogenous guanosine monophosphate (GMP) enhances the stress tolerance of Lactiplantibacillus plantarum Y12. Phenotypic assays demonstrated that GMP supplementation significantly improved biofilm formation, adhesion index, and auto-aggregation ability. The survival ability of Y12 in simulated gastric juice, intestinal juice, and freeze-drying stress was also significantly increased. Transcriptomic results revealed that GMP increased the intracellular content of the second messengers C-di-AMP and C-di-GMP by reducing phosphodiesterase (PDE, RS04640). This, together with the upregulated expression of luxR and rpoN, synergistically promoted biofilm formation. Furthermore, GMP enhanced acid tolerance by increasing glutamate decarboxylase activity (GAD, RS05235). It also significantly elevated the levels of extracellular proteins, exopolysaccharides, membrane polysaccharides, and membrane fatty acids by modulating genes related to proteins (yidC, yajC), polysaccharides (agaB, agaC), and membrane fatty acid synthesis (RS02005, plsY), which was also demonstrated by quantitative determination. Collectively, these regulatory mechanisms substantially improve the stress tolerance of L. plantarum Y12, providing a theoretical basis for its application.