Preventive Effects of Probiotic Formula on Metabolic Stress Associated Physical Fatigue in Forced Swimming and LPS-Induced Mouse Models

Abstract:

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex disorder characterized by persistent fatigue and post-exertional symptom exacerbation, frequently associated with immune and metabolic disturbances. To evaluate the therapeutic potential of a probiotic formula, HH-205M, we employed a composite mouse model combining forced swimming stress (FSS) and repeated lipopolysaccharide (LPS) administration. FSS-LPS exposure induced pronounced fatigue-like phenotypes, including reduced physical endurance capacity in treadmill and weight-loaded swimming tests, delayed recovery in post-swim grooming behavior, and increased thermal pain sensitivity.

These behavioral impairments were accompanied by elevated serum creatine kinase (CK), lactate dehydrogenase (LDH), and lactate levels, indicating systemic metabolic stress. At the tissue level, FSS-LPS increased lipid peroxidation and upregulated pro-inflammatory cytokine expression while suppressing antioxidant gene expression in the gastrocnemius muscle. Furthermore, expression of lactate-related genes, Hcar1 (GPR81) and Slc16a1 (MCT1), was reduced, suggesting disruption of lactate transport and sensing pathways under chronic stress and inflammatory conditions.

HH-205M supplementation attenuated the elevations in circulating fatigue-related biomarkers, moderated oxidative and inflammatory responses, and restored Hcar1 and Slc16a1 expression.

These molecular changes were paralleled by improvements in endurance performance and nociceptive sensitivity. HH-205M administration was also associated with distinct shifts in gut microbial composition, including enrichment of Akkermansia and Bacteroides and reduced relative abundance of Alistipes.

Collectively, these findings indicate that the FSS-LPS composite model recapitulates inflammation-associated metabolic disturbances relevant to fatigue-like conditions and that HH-205M administration is associated with concurrent improvements in behavioral and molecular parameters in this model.

Source: Song JG, Bae HJ, Lee DH, Seo J, Lee B, Shin KJ, Chung EC, Lee J, Kim HW, Oh NS. Preventive Effects of Probiotic Formula on Metabolic Stress Associated Physical Fatigue in Forced Swimming and LPS-Induced Mouse Models. J Microbiol Biotechnol. 2026 Apr 10;36:e2603034. doi: 10.4014/jmb.2603.03034. PMID: 41958144. https://pubmed.ncbi.nlm.nih.gov/41958144/

Integrated ‘omics analysis for the gut microbiota response to moxibustion in a rat model of chronic fatigue syndrome

Abstract:

Objective: To observe the efficacy of moxibustion in the treatment of chronic fatigue syndrome (CFS) and explore the effects on gut microbiota and metabolic profiles.

Methods: Forty-eight male Sprague-Dawley rats were randomly assigned to control group (Con), CFS model group (Mod, established by multiple chronic stress for 35 d), MoxA group (CFS model with moxibustion Shenque (CV8) and Guanyuan (CV4), 10 min/d, 28 d) and MoxB group (CFS model with moxibustion Zusanli (ST36), 10 min/d, 28 d).

Open-field test (OFT) and Morris-water-maze test (MWMT) were determined for assessment the CFS model and the therapeutic effects of moxibustion.16S rRNA gene sequencing analysis based gut microbiota integrated untargeted liquid chromatograph-mass spectrometer (LC-MS) based fecal metabolomics were executed, as well as Spearman correlation analysis, was utilized to uncover the functional relevance between the potential metabolites and gut microbiota.

Results: The results of our behavioral tests showed that moxibustion improved the performance of CFS rats in the OFT and the MWMT. Microbiome profiling analysis revealed that the gut microbiomes of CFS rats were less diverse with altered composition, including increases in pro-inflammatory species (such as Proteobacteria) and decreases in anti-inflammatory species (such as Bacteroides, Lactobacillus, Ruminococcus, and Prevotella). Moxibustion partially normalized these changes in the gut microbiota.

Furthermore, CFS was associated with metabolic disorders, which were effectively ameliorated by moxibustion. This was demonstrated by the normalization of 33 microbiota-related metabolites, including mannose (P = 0.001), aspartic acid (P = 0.009), alanine (P = 0.007), serine (P = 0.000), threonine (P = 0.027), methionine (P = 0.023), 5-hydroxytryptamine (P = 0.008), alpha-linolenic acid (P = 0.003), eicosapentaenoic acid (P = 0.006), hypoxanthine (P = 0.000), vitamin B6 (P = 0.000), cholic acid (P = 0.013), and taurocholate (P = 0.002).

Correlation analysis showed a significant association between the perturbed fecal microbiota and metabolite levels, with a notable negative relationship between LCA and Bacteroides.

Conclusions: In this study, we demonstrated that moxibustion has an antifatigue-like effect. The results from the 16S rRNA gene sequencing and metabolomics analysis suggest that the therapeutic effects of moxibustion on CFS are related to the regulation of gut microorganisms and their metabolites. The increase in Bacteroides and decrease in LCA may be key targets for the moxibustion treatment of CFS.

Source: Chaoran LI, Yan Y, Chuwen F, Heng LI, Yuanyuan QU, Yulin W, Delong W, Qingyong W, Jing G, Tianyu S, Xiaowei S, Xue W, Yunlong H, Zhongren S, Tiansong Y. Integrated ‘omics analysis for the gut microbiota response to moxibustion in a rat model of chronic fatigue syndrome. J Tradit Chin Med. 2023 Oct;43(6):1176-1189. doi: 10.19852/j.cnki.jtcm.20231018.004. PMID: 37946480; PMCID: PMC10623263. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10623263/ (Full text)