Jingjing He

Background/Objectives: Fruit juice is commonly consumed with meals, yet its liquid matrix and rapidly absorbable carbohydrates may influence postprandial glycemic excursions. Whether altering the timing of fruit juice intake relative to a meal can attenuate postprandial glucose (PPG) remains unclear. This study aimed to investigate the effect of the timing of apple juice consumption on PPG in healthy adults. Methods: This randomized, two-period crossover trial (ChiCTR2600121025) enrolled 20 healthy adults in Beijing, China (March 2026), randomized 1:1; 19 with valid continuous glucose monitoring (CGM) data were analyzed. Each consumed 200 mL of 100% apple juice either 30 min before a standardized breakfast (preload) or with the same breakfast (co-ingestion), separated by a 4-day washout. Standardized lunch and dinner were provided. Blinding was not feasible. The primary outcome was breakfast peak glucose measured by CGM; secondary outcomes were incremental area under the curve (iAUC_0–210), maximum excursion, and the corresponding lunch and dinner outcomes. Results: Preloading significantly reduced breakfast peak glucose versus co-ingestion (mean difference 0.51 mmol/L; 95% confidence interval [CI] 0.07–0.94; p = 0.025) and breakfast maximum glucose excursion (0.42 mmol/L; 95% CI 0.02–0.82; p = 0.040), but not iAUC_0–210 (0.07 mmol/L·h; 95% CI −0.57 to 0.70; p = 0.830); no glycemic outcome differed at lunch or dinner. Conclusions: Consuming the same serving of apple juice 30 min before breakfast, rather than with it, reduced breakfast peak glucose and maximum glucose excursion. For individuals who already consume fruit juice, adjusting its timing relative to breakfast reduced breakfast peak glucose and maximum glucose excursion in this small sample; confirmation in larger trials is needed.

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.

Background: Functional constipation is a common gastrointestinal disorder that impairs quality of life. Although probiotics have shown benefits in constipation, whether live and heat-killed forms of the same strain act through similar mechanisms remains unclear. This study compared the effects of live and heat-killed Lacticaseibacillus paracasei K56 in experimental constipation. Methods: Loperamide-treated mice received live or heat-killed L. paracasei K56. Gastrointestinal motility, colonic histology, neurotransmitters, aquaporin expression, gut microbiota, short-chain fatty acids, and metabolomic profiles were evaluated. Results: Both preparations relieved constipation, as reflected by shorter defecation latency, increased fecal output and moisture, and faster intestinal transit, with live K56 producing greater improvement. Colonic injury was alleviated, accompanied by reduced Aqp2 and Aqp3 expression and normalization of 5-hydroxytryptamine, substance P, and vasoactive intestinal peptide. The treatments increased Lactobacillus and Lachnospiraceae, promoted butyrate production, and altered tryptophan metabolism. Heat-killed K56 was mainly associated with changes in phenylalanine/tyrosine- and methionine-related metabolism, whereas live K56 showed more pronounced alterations in arginine/polyamine, tryptophan, and bile acid metabolism. Conclusions: Live and heat-killed L. paracasei K56 improved constipation through shared and distinct mechanisms involving gut microbiota, microbial metabolism, enteric neurotransmission, and intestinal water homeostasis. Live K56 produced stronger effects, whereas heat-killed K56 retained substantial biological activity.

Background/Objectives: Functional constipation (FC) commonly affects middle-aged and older adults, but current pharmacological treatments have limitations. Postbiotics may offer safety advantages, but clinical evidence is limited. This randomized controlled trial evaluated the efficacy and safety of a heat-inactivated two-strain Lacticaseibacillus paracasei fermented milk in adults with FC. Methods: One hundred adults aged 45–75 years with Rome IV-defined FC received the fermented milk or placebo for 4 weeks. The primary outcome was the change in weekly spontaneous bowel movement (SBM) frequency from baseline to week 4. Secondary outcomes included complete spontaneous bowel movement (CSBM) frequency, whole-gut transit time (WGTT), constipation symptom scores, quality of life, serum biomarkers, and adverse events. Primary analysis was per-protocol (n = 96); intention-to-treat analysis was applied to primary and key secondary outcomes. Results: Dropout was 4% (n = 4, 2 per group), and adherence was >80% in both groups. The intervention showed no significant benefit over placebo for the primary outcome or for most secondary clinical outcomes. Although both groups improved within-group, no significant between-group differences were observed at week 4 for changes in SBM (MD = −0.14, 95% CI: −0.85, 0.57; p = 0.683), CSBM (MD = 0.27, 95% CI: −0.61, 1.15; p = 0.543), or WGTT (MD = −1.55 h, 95% CI: −7.65, 4.55; p = 0.614). Symptom and quality-of-life scores also did not differ between groups. Exploratory biomarker analyses showed significantly greater increases in serum VIP and ACh in the intervention group (VIP: MD = 105.23 ng/L, p < 0.001; ACh: MD = 42.95 ng/L, p = 0.035). No adverse events were reported. Conclusions: Four weeks of this postbiotic was safe but did not significantly improve bowel function or symptoms in the overall FC population. The increases in serum VIP and ACh suggest engagement of neurotransmitter-related pathways; however, these exploratory findings do not imply causation or clinical efficacy and warrant confirmation in longer-duration trials (Clinical Trial Registry: ChiCTR2500111771).

Background/Objectives: The preschool period is critical for neurodevelopment, yet evidence investigating fortified formula’s effect and potential microbiota–gut–brain axis mechanisms in this age group is limited. To evaluate fortified formula milk’s effect on neurodevelopment and explore potential microbiota–gut–brain axis mechanisms in preschool children. Methods: In this 9-month cluster-randomized, double-blind, controlled trial, 120 healthy children aged 3–6 years from four kindergarten classes were stratified by grade and randomly allocated (1:1) to receive either multi-nutrient fortified formula (intervention, n = 60) or standard control milk (n = 60). Neurocognitive function was assessed using the Wechsler Preschool and Primary Scale of Intelligence, Fourth Edition (WPPSI-IV). Safety was evaluated through anthropometry and blood biochemistry. Gut microbiota (16S rRNA sequencing) and fecal metabolomes (untargeted LC-MS) were analyzed at baseline and 9 months. Results: The intention-to-treat (ITT) analysis showed no significant difference in Full Scale Intelligence Quotient (adjusted mean difference: 1.05 points; 95% CI: −1.42, 3.52; p = 0.400). However, the intervention group significantly improved the Processing Speed Index (adjusted mean difference: 5.91 points; 95% CI: 1.88, 9.93; p = 0.004), increased gut microbial alpha diversity (Shannon index) and Bifidobacterium abundance. Metabolomic analysis revealed elevated fecal 2-hydroxybutyric acid (2-HB), a marker of propanoate metabolism. Increases in both Bifidobacterium and 2-HB levels showed a positive association with PSI improvement (both p < 0.05). All children maintained normal growth and safety parameters. Conclusions: Fortified formula milk improved processing speed in preschoolers, a benefit associated with gut ecosystem modulation characterized by Bifidobacterium enrichment and upregulated microbial propanoate metabolism. These results offer preliminary evidence for the role of the microbiota–gut–brain axis in nutritional cognitive programming during early childhood. (Clinical Trial Registry: ChiCTR2400084211).

Background/Objectives: Current evidence on the diabetes prevention benefit of substituting red meat with white meat remains inconsistent and is predominantly based on Western populations. This research examined whether the benefits of such dietary substitution depend on habitual red meat intake levels. Methods: This prospective analysis included 12,143 adults from the China Health and Nutrition Survey (2004–2015). Dietary intake was assessed by multiple 24 h recalls supplemented by a household food inventory. Incident diabetes was identified via self-report and supplementary biochemical data. Estimates of hazard ratios (HRs) and 95% confidence intervals (CIs) were obtained through Cox proportional hazards modeling. Dose–response relationships were examined using restricted cubic splines. Substitution effects were evaluated within strata defined by baseline red meat intake (p-nonlinearity < 0.0001). Substitution was not associated with diabetes risk in the low-intake stratum (p = 0.107). Conversely, in the high-intake stratum (≥75 g/day), replacing 50 g/day of red meat with white meat was associated with a 34% lower diabetes risk (HR: 0.66; 95% CI: 0.51, 0.86; p = 0.002). Conclusions: Meat intake shows a nonlinear association with diabetes risk in Chinese adults. The potential benefit of substituting white meat for red meat is conditional, with a more pronounced effect observed among individuals with high habitual red meat consumption, which may support the development of targeted dietary guidance for this subgroup.

Instant brown rice lowered postprandial glycemic excursions versus white rice. In postprandial distress syndrome versus healthy controls, glycemic excursions were lower but fullness was greater, suggesting a potential metabolic-symptom trade-off.

Background: Chronic constipation lacks effective long-term treatments. Non-digestible oligosaccharides (NDOs) are short-chain carbohydrates that resist digestion and may improve bowel function. This systematic review and meta-analysis examines the effect of NDOs on constipation-related outcomes in humans. Methods: We searched Ovid MEDLINE, Embase, and Web of Science (2010–May 2025) for randomized controlled trials (RCTs) comparing NDOs with placebo, reporting stool frequency, stool consistency, fecal pH, or short-chain fatty acids (SCFAs). Data were pooled using random-effects meta-analysis. All effect estimates are reported as standardized mean differences (SMDs) with 95% confidence intervals (CIs). Subgroups were analyzed based on baseline constipation status and treatment duration. Results: We included 20 RCTs (1786 participants) evaluating seven NDO types. NDO supplementation significantly increased stool frequency overall, with larger effects in constipated individuals (SMD 0.99, 95% CI 0.58–1.28) than in non-constipated population (SMD 0.30, 95% CI 0.10–0.51). By duration, shorter interventions (≤3 weeks) yielded greater frequency gains (SMD 0.89, 95% CI 0.40–1.38) than longer ones (SMD 0.24, 95% CI 0.09–0.38). While the overall effect on stool consistency was non-significant, constipated patients (SMD 0.46, 95% CI 0.19–0.74) and short-term trials (SMD 0.20, 95% CI 0.03–0.37) showed modest improvements. NDOs also lowered fecal pH (SMD −1.02, 95% CI −1.25–−0.79). Data on SCFAs were inconclusive and based on very limited studies. Conclusions: NDOs modestly increase stool frequency and lower fecal pH, with greater effects in constipated individuals and short-term interventions. However, evidence certainty remains low due to heterogeneity and study limitations. Further studies are needed to establish clinical utility.

Background/Objectives: Dairy and soybean are important potential dietary sources of bone health. However, their comparative effectiveness and the role of specific components remain unclear. In this network meta-analysis (NMA), we aimed to compare the effects of various dairy and soy products (food level) and their key bioactive components (component level) on bone health in healthy women. Methods: We systematically searched PubMed, Embase, Cochrane Library, and Web of Science (up to 28 February 2025) for randomized controlled trials. A frequentist random-effects NMA was used to compare interventions for lumbar spine (LS) and total body (TB) bone mineral density (BMD) and bone turnover markers [osteocalcin (OC), deoxypyridinoline (DPD)]. Mean differences (MDs) and 95% confidence intervals were pooled. Interventions were ranked using the surface under the cumulative ranking curve (SUCRA). Results: Sixty RCTs involving 6284 participants (mean age: 54.2 years) were included. At the food level, no dairy or soy interventions significantly improved outcomes versus control, although milk + yogurt ranked numerically highest based on SUCRA values. At the bioactive-component level, the combination of casein + whey protein (MD 0.04 g/cm², 95% CI 0.01–0.06) and soybean protein (MD: 0.03 g/cm², 95% CI: 0.01–0.05) significantly increased TB BMD. Whey protein alone (SUCRA 74.4% for LS BMD) and casein + whey protein (SUCRA 86.3% for TB BMD and 75.9% for DPD) were among the highest-ranked interventions for bone health. Conclusions: The combination of milk and yogurt may be relatively promising among dairy products for bone health. Whey protein appears to be a key bioactive component beneficial for women’s bone health.