Frontiers in Microbiology
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2025
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IF 4.5
Lin Lin,Siyuan Li,Que Liu,Xingxing Zhang,Ying Xiong,Shaoyun Zhao,Liyue Cao,Jiaxuan Gong,Yaping Liu,Rong Wu
Objective: This study aimed to investigate the potential relation between the retarded growth of skeletal muscle (SM) and dysbiosis of gut microbiota (GM) in children with asthma, and to explore the potential action mechanisms of traditional pediatric massage (TPM) from the perspective of regulating GM and short-chain fatty acids (SCFAs) production by using an adolescent rat model of asthma.Methods: Male Sprague-Dawley rats aged 3weeks were divided randomly into the 5 groups (n=6~7) of control, ovalbumin (OVA), OVA + TPM, OVA + methylprednisolone sodium succinate (MP) and OVA + SCFAs. Pulmonary function (PF) was detected by whole body plethysmograph, including enhanced pause and minute ventilation. Airway allergic inflammation (AAI) status was assessed by concentrations of OVA-specific immunoglobulin E in plasma, interleukin (IL)-4 and IL-1β in bronchoalveolar lavage fluid via ELISA assay. SM mass was assessed by using cross-sectional areas of diaphragm muscle and gastrocnemius via hematoxylin and eosin staining. GM and SCFAs production were detected by 16S rDNA sequencing and GC-MS, respectively. The protein and gene expressions of free fatty acid receptor 2 in SM were detected by using immunohistochemical staining and qRT-PCR, respectively. qRT-PCR was used to detect other relative gene expressions that were closely related with SM mass. The activity of insulin-like growth factor-1 (IGF-1)/protein kinase B (PKB/AKT) pathway in SM was detected by western blotting test.Results: OVA exposure caused obvious AAI and poor PF in adolescent rats. OVA-exposed adolescent rats had a retarded growth of SM mass and inhibited activity of IGF-1/AKT pathway, which was related with GM dysbiosis, reduced SCFAs production and FFAR2 expressions in SM. TPM efficiently enhanced the SM mass, along with alleviating AAI and improving PF. TPM activated IGF-1/AKT pathway in SM, which was closely related with correcting GM dysbiosis, enhanced SCFAs production and FFAR2 expressions.Conclusion: The retarded growth of SM mass and inhibition of IGF-1/AKT pathway existed in OVA-exposed adolescent rats, which was related with GM dysbiosis, reduced SCFAs production and FFAR2 expressions in SM. TPM efficiently enhanced the SM mass, at least, partially via regulating GM, enhancing SCFAs production and activating FFAR2-IGF-1/AKT pathway.
研究领域:
儿科学
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免疫学
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药理学
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微生物学
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肌肉骨骼系统
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高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
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2026
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IF 5.6
Mengnan Zeng,Aozi Feng,Beibei Zhang,Shuna Li,Pengli Guo,Denghui Zhu,Yuhan Zhang,Ziyu Zhang,Qimei Tie,Yanxing Wu,Weisheng Feng,Xiaoke Zheng
Background Allergic asthma is characterized by immune dysregulation and airway inflammation, and increasing evidence implicates gut microbiota-derived metabolites in its pathogenesis. However, the microbial and metabolic mediators underlying the anti-asthmatic effects of natural products remain insufficiently defined. This study investigated the protective effects of a novel triterpenoid (Tri) isolated from Alisma orientale against ovalbumin-induced allergic asthma and explored the underlying mechanisms. Methods The therapeutic effects of Tri were evaluated in ovalbumin-induced allergic asthma mice by assessing airway hyperresponsiveness, histopathological changes, and inflammatory mediators. Gut microbiota depletion, fecal microbiota transplantation, 16S rDNA sequencing, targeted short-chain fatty acid analysis, and lung transcriptomic profiling were performed to characterize microbiota-associated changes related to Tri treatment. In addition, Lactobacillus murinus and acetate intervention experiments were conducted in vivo. A co-culture system of 16HBE cells and bone marrow-derived dendritic cells (BMDCs), together with free fatty acid receptor 2 (FFAR2) silencing or overexpression, was used to further assess the involvement of FFAR2 in the immunoregulatory actions associated with Tri. Results Tri markedly attenuated airway hyperresponsiveness, inflammatory cell infiltration, collagen deposition, and the production of asthma-related inflammatory mediators in asthmatic mice. These protective effects were attenuated after gut microbiota depletion and were partially transferred by fecal microbiota transplantation. Tri restored gut microbial homeostasis, increased the abundance of Lactobacillus murinus , and elevated short-chain fatty acids, particularly acetate. Supplementation with Lactobacillus murinus or acetate reproduced the anti-asthmatic effects of Tri and was associated with upregulation of FFAR2 and restoration of the Th17/Treg balance. In the co-culture system, FFAR2 silencing or overexpression further supported the involvement of FFAR2 in the immunoregulatory effects of Tri and acetate. Conclusion Tri alleviates OVA-induced allergic asthma and is associated with microbiota-derived acetate, enhanced FFAR2-related signaling, and restoration of Th17/Treg balance. These findings suggest that microbiota-derived acetate and FFAR2-related immune regulation may contribute to the anti-asthmatic effects of Tri, although further loss-of-function studies are required to establish direct causality.
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高影响因子
Foods
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2025
·Vol. 14
·期 1
·101
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IF 5.1
Run Yu,Haimeng Zhang,Rui Chen,Yangzhuo Lin,Jingxuan Xu,Ziyang Fang,Yuehang Ru,Chenhan Fan,Guoqing Wu
Alzheimer’s disease (AD) is marked by impaired cognitive functions, particularly in learning and memory, owing to complex and diverse mechanisms. Methionine restriction (MR) has been found to exert a mitigating effect on brain oxidative stress to improve AD. However, the bidirectional crosstalk between the gut and brain through which MR enhances learning and memory in AD, as well as the effects of fecal microbiota transplantation (FMT) from MR mice on AD mice, remains underexplored. In this study, APP/PS1 double transgenic AD mice were used and an FMT experiment was conducted. 16S rRNA gene sequencing, targeted metabolomics, and microbial metabolite short-chain fatty acids (SCFAs) of feces samples were analyzed. The results showed that MR reversed the reduction in SCFAs induced by AD, and further activated the free fatty acid receptors, FFAR2 and FFAR3, as well as the transport protein MCT1, thereby signaling to the brain to mitigate inflammation and enhance the learning and memory capabilities. Furthermore, the FMT experiment from methionine-restricted diet mouse donors showed that mice receiving FMT ameliorated Alzheimer’s learning and memory ability through SCFAs. This study offers novel non-pharmaceutical intervention strategies for AD prevention.
研究领域:
神经科学
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微生物学
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肠脑轴
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代谢组学
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JOURNAL OF ETHNOPHARMACOLOGY
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2024
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IF 4.8
Zihao He,Siyuan Deng,Zhijing Wu,Zheng Cui,Hao Mei,Jinglin Wang,Kaiping Wang,Yu Zhang
Ethnopharmacological relevance Dysfunction of the intestinal barrier was an important trigger for alcoholic liver damage and alcohol had brought about intestinal damage before causing liver damage. The root of Angelica sinensis (Oliv.) Diels, crucial traditional medicinal material, was widely utilized for its blood-invigorating, intestinal-lubricating and gynecological benefits. Angelica sinensis polysaccharide (ASP) was an essential natural active ingredient of Angelica sinensis and exhibited considerable potential for gastrointestinal protection. Nevertheless, the systematic research of ASP on the gastrointestinal tract remained insufficient. Aim of this study To systematically explore the protective effect and underlying mechanisms of ASP against alcohol-induced gastrointestinal injury, including the stomach, ileum and colon. Materials and methods The AFLD mice model was established via the intragastric administration of alcohol twice a day for one week. The protective effect of ASP on the representative segments of the gastrointestinal tract (stomach, ileum and colon) was subsequently studied after confirming its hepatoprotective activity. The impact of ASP on gastrointestinal alcohol metabolism was examined to explain its antioxidant and antiapoptotic activities. Furthermore, the effect of ASP on short-chain fatty acids (SCFA) in the colon and colonic contents was investigated to further enhance the understanding of the underlying mechanisms. Results ASP could reduce oxidative stress and apoptosis in the gastrointestinal tract via regulating CYP2E1-mediated alcohol metabolism. Additionally, ASP could significantly increase the levels of FFAR2, FFAR3 and HCAR2 in colon, thereby promoting the utilization of SCFA. Conclusion ASP was proven for the first time to improve gastrointestinal damage caused by alcohol, indicating its enormous potential as a candidate medicine for the treatment of alcohol related gastrointestinal injury.
研究领域:
药理学
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胃肠病学
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肝病学
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营养保健品
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民族药理学
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BASIC RESEARCH IN CARDIOLOGY
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2026
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IF 9.2
Zhang Qun,Jiang Xue,Liu Lu,Jia Yu-Meng,Yu Pan-Pan,Zhang Jie,Guo Xin-Ying,Wang Jing-Jing,Guo Cai-Xia,Wang Lei
Adverse cardiac remodeling leads to the development of heart failure following myocardial infarction (MI), yet the immunometabolic signals governing early infarct repair remain poorly understood. Short-chain fatty acids (SCFAs) are important immunometabolic regulators, but their relevance and mechanistic contribution to post-MI repair remain unclear. Here, we integrated clinical observations with genetic and pharmacological intervention studies to investigate the role of the SCFAs-free fatty acid receptor 2 (FFAR2) axis in post-MI repair. Circulating SCFAs levels were markedly decreased in patients with MI, and associated with more complex coronary lesions and a higher risk of major adverse cardiovascular events. In murine MI, SCFAs supplementation reduced infarct expansion, cardiomyocyte death, and cardiac rupture, and improved left-ventricular function. These benefits were lost in global and myeloid-specific Ffar2 -deficient mice, demonstrating an essential role for myeloid FFAR2 in SCFA-mediated cardioprotection. Mechanistically, SCFAs activated FFAR2-G αi signaling in macrophages to suppress RANKL–RANK-driven osteoclast-like macrophage differentiation. thereby enhancing early fibrotic stabilization, reducing cardiomyocyte apoptosis, and improving infarct healing. Pharmacological blockade of osteoclast-like macrophage activation partially rescued impaired healing and cardiac dysfunction in myeloid-specific Ffar2 -deficient mice after MI. These findings identify circulating SCFAs as clinically relevant biomarkers associated with coronary lesion complexity and adverse clinical outcomes after MI, and establish the SCFAs–FFAR2 axis as an immune-metabolic pathway that orchestrates macrophage fate and infarct healing. Targeting SCFAs–FFAR2 signaling may represent a therapeutic strategy to limit adverse post-MI remodeling and prevent heart failure.
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高影响因子
Journal of Future Foods
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2026
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IF 7.2
Yihang Zhao,Hangqi Li,Bingkun Bao,Yinzhao Luo,Jingyu Hao,Jun Gong,Sufang Duan,Zhigang Liu
The gut-brain axis is increasingly implicated in Alzheimer's disease (AD), offering a promising target for nutritional interventions. Bovine milk fat globule membrane (BMFGM) is a bioactive component known to modulate gut microbiota and confer neuroprotection. However, the precise molecular mechanisms linking BMFGM to AD amelioration remain elusive. This study demonstrates that BMFGM supplementation significantly improves cognitive performance in 5xFAD transgenic mice, accompanied by reduced amyloid-beta deposition, suppressed neuroinflammation, enhanced brain-derived neurotrophic factor (BDNF) expression, and recovered gut barrier integrity. Importantly, BMFGM significantly reduced interleukin-1β (IL-1β) expression in the colon, serum, and cortex, indicating IL-1β suppression as a central mechanism linking gut, systemic, and neuroinflammation. BMFGM reshaped the gut microbiota and increased fecal butyrate level, which correlated positively with cognitive outcomes. Crucially, antibiotic-induced microbiota depletion or pharmacological blockade of free fatty acid receptor 2 (FFAR2) via GLPG097 abrogated the cognitive, inflammatory, and neuropathological benefits conferred by BMFGM. Collectively, this study elucidates a specific microbiota-metabolite-receptor axis for dietary neuroprotection and highlights butyrate signaling as a critical pathway for AD prevention and management.
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BIOCHEMICAL PHARMACOLOGY
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2026
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IF 6.5
Cheng Cao,Mubin Sun,Jiabao Li,Zhenyu Yuan,Yuwei Gu,Yufan Shao,Lisheng Wang,Xiaohua Jin,Yijie Cheng,Bo Fan
Urate transporter 1 (URAT1, encoded by SLC22A12 ) is a key mediator of renal urate reabsorption and an important pharmacological target for urate-related disorders. Sodium butyrate (BuNa), a gut microbiota derived short-chain fatty acid, has been implicated in host metabolic regulation, but its role in renal urate transport remains unclear. Here, using molecular docking, cellular thermal shift assays, immunoprecipitation-mass spectrometry and multi-omics analyses, we identified free fatty acid receptor 2 (FFAR2) as a direct target of BuNa in renal proximal tubular HK2 cells . BuNa binding upregulated FFAR2 and promoted URAT1 expression and urate uptake via an FFAR2-dependent pathway. Mechanistically, BuNa/FFAR2 signaling acts via GNAQ to activate PLCβ, generating diacylglycerol and engaging a PKC-dependent p38 MAPK/ELK1 cascade that upregulates arrestin beta 2 (ARRB2). ARRB2 directly binds to IκB, preventing its phosphorylation-dependent degradation, thereby stabilizing IκB and inhibiting NF-κB nuclear translocation. Within the SLC22A12 promoter, NF-κB (RELA/p50) and hepatocyte nuclear factor 1 beta (HNF1β) compete for overlapping binding sites. By blocking NF-κB nuclear entry, BuNa relieves this competition, permitting HNF1β-driven SLC22A12 transcription. Thus, BuNa enhances URAT1-mediated urate reabsorption in HK2 cells via an FFAR2/GNAQ/p38 MAPK/ELK1/ARRB2 axis that stabilizes IκB, suppresses NF-κB, and relieves the competitive binding between NF-κB and HNF1β on the SLC22A12 promoter. These findings establish a previously unrecognized gut microbiota–kidney axis linking microbial BuNa to renal urate homeostasis through a novel transcriptional regulatory circuit.
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