Intraoral halitosis is predominantly caused by anaerobic microbes within the tongue biofilm that break down sulfur-containing amino acids, especially cysteine and methionine, to volatile sulfur compounds (VSCs). In addition to microbial activity, there is growing evidence to suggest that dietary factors are able to influence VSC formation by affecting substrate availability, redox equilibrium, and oral ecological stability and that some of these effects are due to extraoral metabolic activity. This review integrates food chemistry, microbial ecology, and oral health to explain how dietary exposures can interact with the oral microbiome to trigger and maintain halitosis. We synthesize current evidence on tongue biofilm ecology, key microbial taxa and metabolic pathways, and the modifying roles of salivary flow, periodontal inflammation, and common beverages and condiments. Diagnostic approaches are discussed with a mechanistic viewpoint, which has focused on combined organoleptic, gas specific analysis, tongue biofilm imaging, and selective provocation testing. Comprehensively, halitosis is presented as a diet modifiable, ecology-driven disease, the diagnostics of which should be guided by phenotype, and the intervention based on microbiomes and tailored care plans should be sustainable so that evidence-based functional foods and personalized care plans can be developed.
Chronic kidney disease (CKD) is associated with the accumulation of protein-bound uremic toxins (PBUTs), which cause cardiovascular dysfunction via oxidative stress, inflammation, and fibrosis. Indole-3-acetic acid (IAA), a uremic toxin generated from the gut microbiota, has been identified as a key modulator of cardiovascular injury in CKD. This study looked at the therapeutic efficacy of a 10% docosahexaenoic acid (DHA) supplemented diet paired with captopril (100 mg/kg) in CKD rats exposed to IAA (50 mg/kg) for 30 days. DHA alone enhanced IAA clearance and lowered systemic levels, while the DHA + captopril combination offered the most cardio-protection. Serum troponin-I, CK-MB, and lactate dehydrogenase (LDH) levels were significantly reduced, while antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT) were protected. Gene expression analysis revealed lower levels of heart hypertrophic (ANP, BNP, β-MHC) and fibrotic (Col-I, Col-III) markers, which align with the histological findings of reduced myocardial fibrosis and structural preservation. The co-treatment reduced inflammation by inhibiting the AhR-NF-κB signaling pathway and TNF-α expression. These findings demonstrate that DHA in combination with captopril mitigates IAA-induced cardiovascular damage in CKD and represents a promising adjunct strategy to reduce cardiovascular complications in uremic condition.
Theabrownin (TB) is a bioactive compound derived from tea. Alcoholic liver disease (ALD), caused by chronic alcohol consumption, leads to progressive liver damage associated with inflammation and steatosis. This study aimed to investigate TB's protective effects against ALD and elucidate its mechanisms. A chronic-binge ethanol feeding model was used to induce ALD in mice. Mice were administered TB alongside ethanol exposure. Liver function markers, oxidative stress parameters, inflammatory cytokines, and apoptosis indicators were evaluated. Intestinal barrier integrity and gut inflammation were assessed, along with the expression of tight junction proteins. 16S rRNA sequencing was performed to analyze gut microbiota composition. TB supplementation significantly alleviated hepatic oxidative stress and inflammation and decreased hepatocellular apoptosis. In the gut, TB mitigated ethanol-induced inflammation and restored barrier function by enhancing tight junction protein expression. Microbiota analysis revealed that TB notably increased the abundance of Akkermansia muciniphila, which was associated with altered tryptophan metabolism and activation of the aryl hydrocarbon receptor (AhR) signaling pathway. These changes contributed to the overall protective effect of TB against alcohol-induced toxicity. TB exhibits nutritionally relevant hepatoprotective effects through its antioxidant properties, enhancement of gut barrier integrity, and modulation of the gut microbiota and metabolite-mediated signaling pathways. These findings support the potential of TB as a dietary intervention for preventing or managing ALD.
In this study, we investigated and compared the anticarcinogenic efficacy of plant-derived α-linolenic acid (P-ALA) and marine-derived α-linolenic acid (M-ALA) using MCF-7 breast cancer cell line and mammary gland carcinoma model induced by N-methyl-N-nitrosourea (MNU). In vitro MTT assessment on ER+ MCF-7 cells exhibited significant cell viability with P-ALA (IC505.57 µM) when compared with M-ALA (IC505.91 µM) and tamoxifen (TAM) (IC50 9.16 µM). Mitochondrial-mediated apoptosis with apoptotic changes were more evident after P-ALA treatment when scrutinized using DAPI, JC-1, and AO/EtBr staining. The P-ALA (p > 0.001***) and M-ALA (p > 0.001***) reversed the cachexia associated with MNU and positively restored lipid profiles (↓TG, ↓LDL, ↓VLDL, and ↑HDL) (p > 0.001***). ECG and HRV analysis showed that P-ALA-HD effectively restored autonomic functions. Lactate analysis P-ALA-HD significantly reduced lactate accumulation. Immunoblotting indicated upregulation of pro-apoptotic (BAX; BAD and caspase-3 at p > 0.001***) and down-regulation of Bcl-2 (p > 0.001***). P-ALA also inhibited lipogenesis (↓SREBP-1c and FASN↑; p > 0.001***), glucose and lactate transport (GLUT-1↓, MCT-1 ↓, and MCT-4↓ at p > 0.001***), hypoxic signaling (↓HIF-1α p > 0.001*** and ↑PHD2 p > 0.001***), and intrinsic mitochondrial apoptotic marker (VDAC-1↓p > 0.001***). P-ALA demonstrated anticancer, lipid-modulating, and cardioprotective that underscore the potential of P-ALA as efficacious and sustainable therapeutic approach for management of breast cancer.
Postbiotics, composed of inanimate microorganisms or their components, are gaining attention for managing intestinal discomfort, being safer than probiotics for vulnerable patients. This study investigates the effects of short-term consumption of a heat-stabilized VSL#3 formulation (VSL#3-HS) in a mouse model of dextran sulphate sodium (DSS)-induced colitis. Male C57BL/6 mice were divided into four groups: (1) Placebo (PLA); (2) VSL#3-HS (1 × 109 cells/mouse/day for 7 days); (3) DSS + PLA (2% DSS in drinking water from days 1-7, PLA from days 4-10); (4) DSS + VSL#3-HS (2% DSS from days 1-7, VSL#3-HS from days 4-10). All mice were euthanized on day 11 for tissue collection. VSL#3-HS rapidly alleviated clinical signs of the disease, including improvements in disease activity index and colon length. This effect was accompanied by a reduction in colonic pro-inflammatory mediators (IL-6, TNF-α, IL-1β) and a partial restoration of occludin gene expression in the intestine. However, no improvement was observed in MPO activity or microscopic tissue damage. The experimental findings demonstrate the efficacy of postbiotics in a murine model of UC and support further investigation into the efficacy of the heat-stabilized VSL#3-HS formulation to assess its potential applicability in human studies.
Bee Bread (BB), a fermented bee product rich in antioxidant compounds, exerts protective effects against diabetes-associated small intestinal damage. This study investigated the effects of BB on small intestinal morphology, mucosal integrity, and antioxidant enzyme activity in streptozotocin (STZ)-induced diabetic rats. Forty Wistar albino rats were randomly divided into five groups: control, sham (50 mg/kg sodium citrate), diabetes (DM; 50 mg/kg STZ), BB (100 mg/kg), and Diabetes + Bee Bread (DM+BB). After 15 days, intestinal tissues were examined using histopathological, immunohistochemical (IHC), and scanning electron microscopy (SEM) analyses. Diabetic rats exhibited hyperglycemia (363.63 ± 14.64 mg/dL vs. 97.25 ± 2.71 mg/dL in controls at day 15; p < 0.001), weight loss, villus elongation, epithelial desquamation, and mucosal disorganization. BB supplementation reduced blood glucose levels (approximately 15%-16% in the DM+BB group), attenuated weight loss, and preserved small intestinal architecture, with significant differences in villus length among groups (p < 0.05). Mn-SOD immunoreactivity showed no significant differences among groups (p > 0.05), although redistribution was observed in diabetic tissues. CAT immunoreactivity remained weak and unchanged across groups. SEM analysis confirmed improved villus architecture and preserved goblet cell morphology following BB treatment. BB attenuated diabetes-induced small intestinal injury and preserved intestinal mucosal architecture, findings that may be associated with localized adaptive redox responses.
Neurological diseases such as Alzheimer's disease, Parkinson's disease, Huntington's disease, multiple sclerosis, retinal neurodegeneration, and spinal cord injury represent a growing global health burden with limited therapeutic options. Natural compounds, particularly flavonoids, have emerged as promising neuroprotective agents. Naringenin (NAR), a citrus-derived flavanone, exhibits potent antioxidant, anti-inflammatory, and neuroprotective properties. Recent studies revealed that NAR modulates multiple cellular pathways, including oxidative stress reduction, mitochondrial protection, autophagy induction, inhibition of microglial activation, and suppression of neuroinflammatory signaling such as NF-κB and NLRP3 inflammasome. Furthermore, NAR has demonstrated the ability to reduce amyloid-β plaque deposition, inhibit α-synuclein aggregation, preserve dopaminergic neurons, modulate immune responses in multiple sclerosis, and improve functional recovery after spinal cord injury. This review comprehensively summarizes the mechanistic insights and therapeutic potential of NAR across various neurodegenerative diseases, highlighting its promise as a multifunctional neuroprotective agent and the need for further translational research.
Vitamin D (VD) deficiency is prevalent globally. To improve dietary recommendations for food fortification, we used male rats fed with diets depleted of VD or supplemented/rehabilitated with either vitamin D2 or vitamin D3 or combination, and compared their impact on calcium homeostasis, skeletal muscle and heart. Body composition was assessed by DEXA, muscle strength by grip test. Serum calcium, parathyroid hormone and 25-hydroxyvitamin D [25(OH)D] were measured using standard methods. Skeletal muscle and left ventricle were used for histopathology; RNA and protein were extracted for analysis of gene expression and enzymatic activity, respectively. 25-hydroxylated form of D3 was significantly higher than that of D2 in serum. D2 was less efficacious than D3 at improving skeletal muscle fiber size, strength, expression of contractility genes [Myh2, Tnnc1] and metabolic enzymes [Cs, β-Had]. Under maintenance cardiac contractility gene expression [Myh7 & Serca2a] was comparable between the D2 and D3 groups, though 400 IU D2 notably suppressed Serca2 expression. Post-rehabilitation, the 2000 IU D3 group demonstrated significant improvement in these genes. Overall, our study demonstrates similar efficacy of D2 and D3 at regulating calcium homeostasis, but a better efficacy of D3 than D2 on structure, function and energy metabolism of skeletal muscle and heart.
Asthma remains a prevalent global health challenge, necessitating novel therapeutic targets. This study hypothesized that pear polysaccharide alleviates asthma by modulating ferroptosis-related biomarkers. We integrated transcriptomic data (GSE143303, GSE147878) with database mining (CTD, OMIM, GeneCards, HERB, and FerrDb) to identify genes shared among asthma, pear, and ferroptosis. Machine learning screened core biomarkers, validated in independent datasets (GSE43696 and GSE63142). An ovalbumin-induced asthma mouse model was used to test the effect of Korla fragrant pear polysaccharide (10 and 40 mg/kg). Bioinformatics analysis identified 146 asthma-pear shared genes enriched in oxidative stress. Seven biomarkers (AR, CDKN1A, HMOX1, IL1B, IL6, PARP1, and TP53) were screened. In vivo, pear polysaccharide significantly attenuated cytokine release, and reversed the expression of the seven biomarkers in lung tissue and BALF of murine asthma model.Our study demonstrates that pear polysaccharide alleviates asthma pathology, potentially by targeting a hub gene network centered on ferroptosis-related biomarkers.
Obesity in women of reproductive age is often associated with low-grade inflammation and functional iron deficiency. Epigallocatechin gallate (EGCG), a major green tea catechin, has antioxidant, anti-inflammatory, and metabolic-regulating properties but may also interfere with iron absorption. This randomized, double-blind, placebo-controlled pilot study evaluated the effects of EGCG on lipid profile, inflammation, iron status, and plasma metabolomics in women with obesity. Seventeen participants (BMI ≥30 kg/m2; age 20-44 years) received 400 mg/day EGCG (green tea extract: 98% polyphenols, 60% catechins, ∼50% EGCG) or placebo for eight weeks. Outcomes included serum lipids, inflammatory markers (CRP, IL-6, TNF-α, IL-10), iron indices (ferritin, hepcidin, serum iron, transferrin saturation), glucose, and metabolomics. No between-group difference remained significant after correction for multiple comparisons. Total cholesterol (β = -10.9 mg/dL; p = 0.16) and LDL-C (β = -9.7 mg/dL; p = 0.16) showed decreases, and IL-6 the largest, though nonsignificant, reduction (p = 0.09); other cytokines and glucose were unchanged. Metabolomics identified 29 nominally differential metabolites enriched in lipid metabolism, plasmalogen biosynthesis, and mitochondrial β-oxidation, none surviving FDR correction. Iron status was stable. These findings suggest metabolic effects of EGCG and support short-term safety at 400 mg/day. Larger, longer trials with targeted metabolomics are warranted.
Cisplatin-induced acute kidney injury (AKI) is a dose-limiting chemotherapy complication laking effective clinical interventions. This study investigated the protective mechanisms of proanthocyanidins (PACs), a promising food-derived polyphenol, against cisplatin-induced systemic toxicity in C57BL/6 mice. Multi-omics integration combining 16S rRNA sequencing and renal transcriptomics, was employed to identify microbial-metabolic signaling nodes. Notably, 7-day PAC pretreatment (25 or 50 mg/kg/day) significantly alleviated renal dysfunction, normalized serum creatinine, blood urea nitrogen, reinforced renal antioxidant defenses, and suppressed kidney inflammation. Transcriptomic profiling revealed that cisplatin-induced renal damage was associated with the dysregulation of the cAMP signaling pathway, which was effectively reversed by PACs. Furthermore, 16S rRNA sequencing revealed that PACs restructured the gut microbiota by suppressing the pathogenic taxa (Alistipes and CAG_485) and enriching beneficial taxa (Muribaculaceae). Integrated network analysis further linked these microbial shifts to the stabilization of renal cAMP signaling and redox homeostasis, suggesting a coordinated gut-kidney crosstalk. In conclusion, PACs function as a multifaceted food-derived adjuvant that potentially attenuates cisplatin-induced AKI, providing a molecular framework for gut-targeted nutritional intervention in chemotherapy-induced systemic toxicity.
Food-derived bioactive components play a crucial role in the prevention of cardiovascular diseases. Daidzein (DAI), a soy isoflavone, possesses notable cardioprotective potential; however, its precise role in nicotine-induced atherosclerosis (AS) and its underlying mechanisms remain unclear. This study explored whether DAI protects against AS by modulating macrophage pyroptosis and lipid metabolism via redox-sensitive signaling pathways. In human acute monocytic leukemia cell line (THP-1)-derived macrophages, DAI alleviated nicotine-induced pyroptosis, as evidenced by the downregulation of NOD-like receptor family pyrin domain-containing 3 (NLRP3), ASC, cleaved caspase-1, and gasdermin D (GSDMD)-N, accompanied by reduced secretion of interleukin (IL)-1β, IL-6, and IL-18, and decreased lactate dehydrogenase (LDH) release and caspase-1 activity. DAI also enhanced (7-nitrobenz-2-oxa-1,3-diazole)-cholesterol (NBD)-cholesterol efflux, suppressed DiI-labeled oxidized low-density lipoprotein (DiI-ox-LDL) uptake, and mitigated intracellular lipid droplet accumulation. Mechanistically, silencing nuclear factor erythroid 2-related factor 2 (Nrf2), inducing reactive oxygen species (ROS), or overexpressing thioredoxin-interacting protein (TXNIP) abolished the protective effects of DAI, confirming the involvement of the Nrf2/ROS/TXNIP pathway. In nicotine-exposed apolipoprotein E-deficient (apoE-/-) mice, DAI upregulated vascular Nrf2, downregulated TXNIP and pyroptosis-related proteins, improved plasma lipid profiles, alleviated systemic inflammation, and reduced aortic plaque formation, with no obvious adverse effects observed under the experimental conditions used. Collectively, DAI attenuated macrophage pyroptosis and lipid accumulation via the Nrf2/ROS/TXNIP pathway, thereby mitigating nicotine-induced atherogenesis. These findings provide preclinical evidence for the potential of DAI as a food-derived bioactive compound for smoking-related AS.
High-fat diets (HFDs) disrupt hippocampal (HIP) glutamatergic transmission, reducing synaptic plasticity and contributing to cognitive decline. While excessive dietary fat is known to alter glutamate (Glu) homeostasis, the specific effects of saturated versus unsaturated fatty acids and the role of sex remain unclear. We examined two HFDs, one enriched in oleic acid (OA) (UOLF, unsaturated) and another in palmitic and lauric acids (LAs) (SOLF, saturated), in young adult male and female mice. In males, both diets increased HIP Glu and glutamine (Gln) levels; however, only UOLF upregulated genes linked to Glu/Gln uptake and synthesis, suggesting an adaptive metabolic response. These changes were absent in females, indicating marked sex-dependent effects. In cultured HIP neurons and astrocytes, OA caused milder alterations than palmitic acid (PA) and selectively activated pathways that may lower extracellular Glu and enhance recycling. Lauric acid (LA) failed to activate protective mechanisms, implying it is a major driver of HIP dysfunction in males consuming saturated fats. Both diets disrupted the HIP Glu-Gln cycle in males, but only unsaturated fats triggered compensatory mechanisms that mitigate Glu accumulation. These findings emphasize the critical role of dietary fat composition and biological sex in shaping HIP Glu metabolism and glutamatergic function.
Dietary polyphenols are gaining attention as regulators of gut-brain-liver (GBL) signaling in metabolic disease. The objective of this narrative review is to examine how polyphenols affect neuro-metabolic and immune pathways across the gut-brain-liver axis in obesity, type 2 diabetes, and metabolic dysfunction-associated steatotic liver disease. The review covers literature from 2000 to 2025 indexed in PubMed, Scopus, and Web of Science, with emphasis on mechanistic, multi-omics, preclinical, and human studies. Most polyphenols show poor absorption in the gastrointestinal tract and depend on liver enzymes and intestinal microorganisms for conversion into active metabolites, including urolithins, phenyl-γ-valerolactones, equol, and other phenolic acids. These metabolites influence microbial composition, bile acid signaling, gut hormone secretion, and host processes related to oxidative stress, inflammation, energy balance, and mitochondrial function. In animal and cell models, polyphenols reduce hepatic fat accumulation, improve insulin sensitivity, strengthen gut barrier integrity, and lower endotoxemia. Human evidence remains limited, derived mainly from short-term trials with considerable inter-individual variability. This variability appears linked to metabotype, metabolic capacity, habitual diet, sex, and medication use. Overall, current evidence supports polyphenols as multi-target regulators of gut-brain-liver communication. Larger, well-designed clinical and translational studies are needed to confirm their therapeutic relevance.
Diets based on dairy or seafood proteins are reported to be less obesogenic than diets based on terrestrial meat proteins. The metabolic pathways underlying these differences, including processes related to thermogenesis, remain incompletely understood. Here, we investigated responses at levels of the transcriptome and the metabolome associated with potentially obesogenic high-fat, high-protein diets using casein, cod, or chicken as protein sources in mice kept at thermoneutral conditions or room temperature to evaluate metabolic responses to different housing temperatures. By performing plasma metabolomics analyses combined with RNA sequencing and gene set enrichment analyses of liver, muscle, white- and brown adipose tissue, we aimed to decipher the metabolic output and pathways modulated by intake of different dietary proteins. Dietary protein intake of casein, cod, or chicken led to differences in obesity development independent of housing temperature. The diet-specific phenotype was associated with a distinct plasma lipid profile and transcriptomic profile in liver and adipose tissue. One-carbon metabolism emerged as a potentially affected key pathway, and the mechanistic target of rapamycin complex 1/2 appeared as a predicted upstream regulator and accordingly suggested to be associated with protein source-dependent differences in obesity development and related metabolic disturbances.
Given the limited knowledge of probiotic effects on clock genes, this study investigated whether probiotics that regulate gut integrity and microbiota balance influence central circadian clock gene expression. In this study conducted on three groups [control group (CG), shifted group (SG), and shifted and probiotic supplement group (SPG)] of eight BALB/c mice each, Clock, Bmal1, and Per2 gene expressions and weight gain were evaluated. Although body weights at baseline, week 8, and week 16 were similar among groups, weight gain over time was significantly higher in the SG and SPG groups (p<0.05). Significant differences were observed between CG and SG at week 8 and between SG and SPG at week 16. Gene expression analyses revealed no significant differences in Clock expression. However, Bmal1 expression at ZT18 was significantly different between the CG and SPG groups (p = 0.045). These findings demonstrate the regulatory effect of probiotic supplementation on circadian disruption and weight gain, suggesting a potential role in circadian rhythm management. Nevertheless, the results should be interpreted cautiously because they are based on limited gene expression changes and require confirmation in larger studies.
Hypertension in the elderly is closely associated with vascular aging, characterized by endothelial dysfunction (ED) and a progressive decline in nitric oxide (NO) bioavailability. Age-related dysfunction of endothelial nitric oxide synthase (eNOS), compounded by increased oxidative stress, creates a vicious cycle of oxidative-nitrosative imbalance, leading to chronic inflammation and arterial stiffness. The Dietary Approaches to Stop Hypertension (DASH) diet was developed as a primary intervention to restore NO balance by protecting endogenous pathways and supplying alternative nitrate-nitrite-NO precursors. However, its cardiovascular benefits are often diminished by age-related alterations in nitrate metabolism and the extensive use of multiple medications in the elderly. Thus, while restoring balance remains a key therapeutic goal, future clinical strategies must evolve from broad dietary recommendations to more personalized, precise nutritional approaches, considering the unique physiological and pharmacological challenges faced by older adults.
Phenolic compounds are recognized for antioxidant, anti-inflammatory, and antidiabetic properties. Lentils are abundant in these compounds, yet comparative studies across varieties and intestinal cells effects remain limited. This study evaluated the nutritional composition, phenolic profile, antioxidant activity, and α-glucosidase inhibition of four lentil types in raw and cooked forms. L01 had the highest bioactive potential and was the only one selected for further evaluation in Caco-2 cells under basal and IL-1β-stimulated conditions. Cooking altered composition, leading to higher protein, fiber, and carbohydrates, reducing tannins, and maintaining high phytic acid in some varieties. L01 consistently showed the highest phenolic content, antioxidant activity, and enzyme inhibition. Its phenolic profile was dominated by kaempferol derivatives, (epi)catechin, and procyanidins, with cooking increasing monomeric catechins but reducing procyanidin oligomers. At noncytotoxic levels, L01 extracts reduced IL-6/8 secretion in stimulated cells, with stronger effects from raw extracts. Additionally, they decreased expression of inflammatory markers (IL-6/8/1β) while increasing expression of metabolic regulation- and barrier-related genes (Peroxisome proliferator-activated receptor-γ, Sirtuin 1, Occludin, and Cadherin-1). Only raw extracts significantly enhanced Heme oxygenase-1 expression under stimulation. These findings highlight compositional differences beyond tegument color and support further investigation of phenolic-rich lentils as potential functional food ingredients targeting gut and metabolic health.
Dietary fiber could inhibit β-carotene bioaccessibility by restricting its release from the food matrix, interfering with digestive enzyme activities, binding bile salts, or modifying viscosity and other physicochemical properties of the digesta. In this study, we investigated whether high methoxyl pectin (HMP), a soluble dietary fiber found in fruits/vegetables and an additive for the food industry would impact β-carotene bioaccessibility under various physiological digestive conditions, following the INFOGEST gastrointestinal model. Concentrations of pancreatin plus bile salts and shear forces (simulated by varying water bath rounds/min. and glass bead addition) were modified in the presence (1.15 mg/mL digesta) and absence of HMP. Endpoints measured in the digesta included β-carotene bioaccessibility, surface tension, viscosity, micelle size, zeta potential, and triglyceride lipolysis. Adding HMP reduced overall bioaccessibility of β-carotene from 32.1±6.2% to 24.1±5.7% (p<0.001). All other parameters also had a significant impact on the bioaccessibility of β-carotene, that is, bile/pancreatin concentration (p<0.001), water bath shaking speed (p<0.001), and glass beads (p = 0.001). Surface tension, viscosity, and micelle size were less strongly affected by HMP addition (p<0.05), though not triglyceride lipolysis. The inhibitory effect of HMP varied depending on bile/pancreatin concentration and shear-forces, with strongest reductions when β-carotene bioaccessibility was highest at onset.
Rheumatoid arthritis (RA) is an autoimmune disease closely associated with gut microbiota dysbiosis. Amid growing interest in microbial-derived therapeutics, postbiotics, defined as preparations of nonliving microorganisms and/or their components conferring host benefits, have emerged as candidates. However, the immunomodulatory potential of Bifidobacteria postbiotics in RA remains unexplored. This study investigated the effects of heat‑killed Bifidobacterium longum ZFML0012 (HK‑B. longum) on RA and its underlying mechanisms using in vitro and in vivo models. In LPS-induced cells, HK-B. longum significantly suppressed the expression of pro-inflammatory cytokines such as IL-1β and TNF-α while promoting the anti-inflammatory factor IL-10. In collagen-induced arthritis (CIA) mice, it reduced arthritis scores, joint swelling, and bone erosion. Mechanistically, HK-B. longum remodeled gut microbiota, increased SCFAs (acetate and butyrate), and particularly upregulated the immunomodulatory metabolite L-Glutamine in both gut and serum. In vitro experiments confirmed that L-Glutamine inhibited TNF‑α‑induced inflammation, abnormal proliferation, and migration in MH7A synovial cells. Meanwhile, HK‑B. longum regulated the T helper cell 17/Regulatory T cell (Th17/Treg) immune imbalance, modulated local inflammatory factors, and restored the osteoprotegerin/receptor activator of nuclear factor‑κB ligand (OPG/RANKL) ratio in joints. These findings provide new evidence for using postbiotics to alleviate RA through gut-joint axis regulation.
