Probiotics could improve cognitive functions in patients with neurological disorders such as Alzheimer’s disease, but the effects on cognitive function in healthy older adults without cognitive impairment need further study. The purpose of this study was to investigate the effect of Bifidobacterium longum BB68S (BB68S) on cognitive functions among healthy older adults without cognitive impairment. A randomized, double-blind, placebo-controlled trial was conducted with 60 healthy older adults without cognitive impairment who were divided into probiotic or placebo groups and required to consume either a sachet of probiotic (BB68S, 5 × 10¹⁰ CFU/sachet) or placebo once daily for 8 weeks. The Montreal Cognitive Assessment (MoCA) was used as an inclusion screening tool to screen elderly participants with healthy cognitive function in our study, and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) was used to assess cognitive function in subjects before and after intervention as an assessment tool. BB68S significantly improved subjects’ cognitive functions (total RBANS score increased by 18.89 points after intervention, p < 0.0001), especially immediate memory, visuospatial/constructional, attention, and delayed memory domains. BB68S intervention increased the relative abundances of beneficial bacteria Lachnospira, Bifidobacterium, Dorea, and Cellulosilyticum, while decreasing those of bacteria related to cognition impairment, such as Collinsella, Parabacteroides, Tyzzerella, Bilophila, unclassified_c_Negativicutes, Epulopiscium, Porphyromonas, and Granulicatella. In conclusion, BB68S could improve cognitive functions in healthy elderly adults without cognitive impairment, along with having beneficial regulatory effects on their gut microbiota. This study supports probiotics as a strategy to promote healthy aging and advances cognitive aging research.

Current treatment for functional dyspepsia (FD) has limited and unsustainable efficacy. Probiotics have the sustainable potential to alleviate FD. This randomized controlled clinical trial (Chinese Clinical Trial Registry, ChiCTR2000041430) assigned 200 FD patients to receive placebo, positive-drug (rabeprazole), or Bifidobacterium animalis subsp. lactis BL-99 (BL-99; low, high doses) for 8-week. The primary outcome was the clinical response rate (CRR) of FD score after 8-week treatment. The secondary outcomes were CRR of FD score at other periods, and PDS, EPS, serum indicators, fecal microbiota and metabolites. The CRR in FD score for the BL-99_high group [45 (90.0%)] was significantly higher than that for placebo [29 (58.0%), p = 0.001], BL-99_low [37 (74.0%), p = 0.044] and positive_control [35 (70.0%), p = 0.017] groups after 8-week treatment. This effect was sustained until 2-week after treatment but disappeared 8-week after treatment. Further metagenomic and metabolomics revealed that BL-99 promoted the accumulation of SCFA-producing microbiota and the increase of SCFA levels in stool and serum, which may account for the increase of serum gastrin level. This study supports the potential use of BL-99 for the treatment of FD.

Oxidative stress is closely linked to aging. Probiotics, whether viable or heat-inactivated, have shown antioxidant properties; however, their effect and mechanism of action in reducing oxidative stress during aging remains underexplored. This study examined the effects of viable and heat-inactivated Lactiplantibacillus plantarum TY-Y10 (L. plantarum TY-Y10) on D-galactose (D-gal)-induced aging in mice, aiming to uncover potential anti-aging mechanisms. Mice were induced to age with D-gal injections, then treated with sodium ascorbate (positive control) or varying doses of L. plantarum TY-Y10 for eight weeks. After treatment, oxidative stress markers, gut microbiota, and liver health were analyzed. Results showed that L. plantarum TY-Y10 decreased malondialdehyde (MDA) and inflammatory markers while increasing antioxidant levels (glutathione, superoxide dismutase, catalase and glutathione peroxidase). Liver damage was reduced, and expression of Nrf2 and related antioxidant enzymes improved. Additionally, L. plantarum TY-Y10 enhanced the abundance of short-chain fatty acid-producing bacteria, boosting fecal short-chain fatty acid levels. In short, both viable and heat-inactivated L. plantarum TY-Y10 mitigated oxidative stress in aging mice by modulating gut microbiota and activating liver antioxidant pathways through the gut-liver axis.

Bifidobacterium longum subsp. infantis YLGB-1496 (YLGB-1496) is a probiotic strain isolated from human breast milk. The application of YLGB-1496 is influenced by carbohydrate utilization and genetic stability. This study used genome sequencing and morphology during continuous subculture to determine the carbohydrate utilization characteristics and genetic stability of YLGB-1496. The complete genome sequence of YLGB-1496 consists of 2,758,242 base pairs, 2442 coding sequences, and a GC content of 59.87%. A comparison of carbohydrate transport and metabolism genes of Bifidobacterium longum subsp. infantis (B. infantis) showed that YLGB-1496 was rich in glycosyl hydrolase 13, 20, 25, and 109 gene families. During continuous subculture, the growth characteristics and fermentation activity of the strain were highly stable. The bacterial cell surface and edges of the 1000th-generation strains were progressively smoother and well-defined, with no perforations or breaks in the cell wall. There were 20 SNP loci at the 1000th generation, fulfilling the requirement of belonging to the same strain. The presence of genes associated with cell adhesion and the absence of resistance genes supported the probiotic characteristics of the strain. The data obtained in this study provide insights into broad-spectrum carbohydrate utilization, genomic stability, and probiotic properties of YLGB-1496, which provide theoretical support to promote the use of YLGB-1496.

The decay of smooth muscle contractility is a major trigger of aging-related intestinal hypomotility, which imposes a substantial healthcare burden. Despite this, effective targeted therapy for this condition remains unavailable. Here, we identified the probiotic Bifidobacterium animalis subsp. lactis BL-99 as a microbiota modulator that restores gut motility through the bile acid (BA)-mediated rescue of smooth muscle contractile function. In a randomized, double-blind clinical trial (ChiCTR2300077583, with the primary endpoint of whole-gut transit time [WGTT], and secondary endpoints including bowel movement frequency, symptom severity, and quality-of-life measures) and naturally aged mouse models, BL-99 intervention significantly reduced the WGTT and concurrently remodeled the gut microbiota. This suppressed bile salt hydrolase-expressing bacteria, which preserved conjugated BA pools, including taurochenodeoxycholic acid (TCDCA). Mechanistic investigations revealed that BL-99 was associated with enhanced expression of the serum response factor (SRF)–myocardin (Myocd) transcriptional axis in colonic smooth muscle cells (SMCs), restoring contractile apparatus components (e.g., α-SMA, SM-MHC). Crucially, TCDCA administration recapitulated BL-99 regulation of intestinal SMC contractile protein expression by inhibiting the PI3K/AKT pathway. Our findings established a microbiota-BA-SMC signaling axis that ameliorates age-related intestinal hypomotility, positioning both BL-99 and TCDCA as precision therapeutic candidates targeting SMC-related dysmotility.