Modulation Of Gut Microbiota Research Articles

Sulforaphane Improves Liver Metabolism and Gut Microbiota in Circadian Rhythm Disorder Mice Models Fed With High-Fat Diets.

This study aims to investigate the effect of sulforaphane (SFN) on hepatic metabolism and gut microbiota in a shifted circadian rhythm (CR) mouse model fed with a high-fat diet (HFD). A shifted CR mouse model with HFD is constructed. Biochemical analyses are used to evaluate the effects of SFN on lipid accumulation and liver function. Targeted metabolomics is used for liver metabolites. Results from hematoxylin and eosin staining and Oil Red O staining show that SFN improves liver lipid accumulation and intestinal inflammatory damage in shifted CR treatment with HFD. The concentrations of amino acid metabolites are increased, and the levels of bile acid metabolites are significantly decreased by SFN treatment. Results from 16S rRNA gene sequencing indicate that SFN modulates gut microbiota, particularly by enhancing beneficial bacteria such as Lachnospiraceae, Lactobacillus, Alistipes, Akkermansia, and Eubacteriaum coprostanoligenes. Correlation analysis confirms a close relationship between intestinal microbiota and hepatic metabolites. SFN significantly regulates CR protein expression in the hypothalamus and liver tissues. SFN alleviates hepatic metabolic disorder and gut microbiota dysbiosis induced by CR disruption under a high-fat diet in a mouse model, indicating the potential of SFN in regulating CR disruption.

In vitro digestion and fecal fermentation behaviors of exopolysaccharide from Morchella esculenta and its impacts on hypoglycemic activity via PI3K/Akt signaling and gut microbiota modulation

This study aimed to evaluate the effects of gastrointestinal digestion on the physicochemical properties and hypoglycemic activity of extracellular polysaccharides from Morchella esculenta (MEPS). The results showed that the MEPS digestibility was 22.57 % after saliva-gastrointestinal digestion and only partial degradation had occurred. Contrarily, after 48 h of fecal fermentation, its molecular weight and molar ratios of the monosaccharide composition varied significantly due to being utilized by human gut microbiota, and the final fermentation rate was 76.89 %. Furthermore, the MEPS-I, the final product of saliva-gastrointestinal digestion still retained significant hypoglycemic activity, it alleviated insulin resistance and increased the IR cells glucose consumption by activating PI3K/AKT signaling pathway. MEPS-I treatment reduced the proportion of Firmicutes to Bacteroidetes, and the relative abundance of beneficial bacteria that enhanced insulin sensitivity and glucose uptake was promoted. This research can provide a theoretical basis for the further development of Morchella esculenta as a health functional food.

Spatiotemporal delivery of multiple components of rhubarb-astragalus formula for the sysnergistic treatment of renal fibrosis.

Rhubarb (Rheum palmatum L.) and astragalus (Radix astragali) find widespread used in clinical formulations for treating chronic kidney disease (CKD). Notably, the key active components, total rhubarb anthraquinone (TRA) and total astragalus saponin (TAS), exhibit superiority over rhubarb and astragalus in terms of their clear composition, stability, quality control, small dosage, and efficacy for disease treatment. Additionally, astragalus polysaccharides (APS) significantly contribute to the treatment of renal fibrosis by modulating the gut microbiota. However, due to differences in the biopharmaceutical properties of these components, achieving synergistic effects remains challenging. This study aims to develop combined pellets (CPs) and evaluate the potential effect on unilateral ureteral obstruction (UUO)-induced renal fibrosis. The CPs pellets were obtained by combining TRA/TAS-loaded SNEDDS pellets and APS-loaded pellets, prepared using the fluidized bed coating process. The prepared pellets underwent evaluation for morphology, bulk density, hardness, and flowing property. Moreover, the in vitro release of the payloads was evaluated with the CHP Type I method. Furthermore, the unilateral ureteral obstruction (UUO) model was utilized to investigate the potential effects of CPs pellets on renal fibrosis and their contribution to gut microbiota modulation. The ex-vivo study demonstrated that the developed CPs pellets not only improved the dissolution of TRA and TAS but also delivered TRA/TAS and APS spatiotemporally to the appropriate site along the gastrointestinal tract. In an animal model of renal fibrosis (UUO rats), oral administration of the CPs ameliorated kidney histological pathology, reduced collagen deposition, and decreased the levels of inflammatory cytokines. The CPs also restored the disturbed gut microbiota induced by UUO surgery and protected the intestinal barrier. The developed CPs pellets represent a promising strategy for efficiently delivering active components in traditional Chinese medicine formulas, offering an effective approach for treating CKD.

Lactobacillus rhamnosus ZJUIDS07 ameliorates type 2 diabetes in mice through the microbiome-gut-pancreas axis

Diabetes mellitus is a chronic metabolic disease characterized by hyperglycemia, with its prevalence escalating. It exerts a profound impact on human health care and socio-economic development. Probiotics, known as natural, safe, and minimal side effects, have emerged as promising intervention agents to manage chronic diabetes. Our study aimed to explore the therapeutic potential of Lactobacillus rhamnosus ZJUIDS07 for mitigating T2D in mice induced by a high-fat diet (HFD) and streptozotocin (STZ). Administration of L. rhamnosus ZJUIDS07 led to a reduction in diabetic symptoms, including reversal of weight loss, improvement in hyperglycemia and insulin resistance, mitigation of disruptions in glucose and lipid metabolism, alleviation of pancreatic pathological damage, and reduction in oxidative stress and inflammation. Moreover, treatment with L. rhamnosus ZJUIDS07 could restore intestinal microbiota balance in T2D mice by altering the structure and composition of intestinal microbiota, and increased short-chain fatty acids (SCFAs) levels. Specifically, L. rhamnosus ZJUIDS07 significantly decreased the abundance of harmful bacteria like Staphylococcus, Corynebacterium, and Odoribacte, while increasing the abundance of beneficial bacteria (especially SCFAs-producing bacteria) such as Muribaculaceae_norank, Dubosiella, Clostridium sensu stricto 1, Lactobacillus, and Faecalibaculum. Our findings highlight that L. rhamnosus ZJUIDS07 represents a promising probiotic strategy for future treatment of T2D, and that the modulation of gut microbiota and their metabolites through the microbiome-gut-pancreas axis play a pivotal role for the antidiabetic effects of L. rhamnosus ZJUIDS07.

Applications of plant-derived extracellular vesicles in medicine.

Plant-derived extracellular vesicles (EVs) are promising therapeutic agents owing to their natural abundance, accessibility, and unique biological properties. This review provides a comprehensive exploration of the therapeutic potential of plant-derived EVs and emphasizes their anti-inflammatory, antimicrobial, and tumor-inhibitory effects. Here, we discussed the advancements in isolation and purification techniques, such as ultracentrifugation and size-exclusion chromatography, which are critical for maintaining the functional integrity of these nanovesicles. Next, we investigated the diverse administration routes of EVs and carefully weighed their respective advantages and challenges related to bioavailability and patient compliance. Moreover, we elucidated the multifaceted mechanisms of action of plant-derived EVs, including their roles in anti-inflammation, antioxidation, antitumor activity, and modulation of gut microbiota. We also discussed the impact of EVs on specific diseases such as cancer and inflammatory bowel disease, highlighting the importance of addressing current challenges related to production scalability, regulatory compliance, and immunogenicity. Finally, we proposed future research directions for optimizing EV extraction and developing targeted delivery systems. Through these efforts, we envision the seamless integration of plant-derived EVs into mainstream medicine, offering safe and potent therapeutic alternatives across various medical disciplines.

Lactiplantibacillus plantarum TCCC11824 exerts hypolipidemic and anti-obesity effects through regulation of NF-κB-HMGCR pathway and gut microbiota in mice and clinical patients

A strong association exists between the high-fat diet (HFD) and the incidence of obesity, hyperlipidemia and cardiovascular disease, affecting an increasing number of individuals. More and more research has shown that probiotics and gut microbiota play important roles in dietary absorption, metabolism and host healthy. This study aims to evaluate the therapeutic effects and the underlying mechanisms of Lactiplantibacillus plantarum TCCC11824 (CGMCC 8198) on hyperlipidemia and obesity in mice and clinical. Fristly, there was a dose-dependent improvement in HFD-induced hyperlipidemia and obesity in mice which had been treated with L. plantarum TCCC11824 for 5 weeks thus restoring the balance of the gut microbiota. Furthermore, it showed that cell lysate of L. plantarum TCCC11824 could directly exhibit protective effects on the hepatocytes steatosis induced by oleic acid, and regulate the expression of HMGCR by inhibiting NF-κB pathway. Importantly, L.plantarum TCCC11824 ameliorated the expression of indicators of hyperlipidemia and inhibited the synthesis of SCFAs (short-chain fatty acids), as shown by blood and fecal tests in hyperlipidemic patients. In summary, L. plantarum TCCC11824 exerts anti-hyperlipidemic and anti-obesity effects through the regulation of HMGCR via NF-κB and modulating gut microbiota, indicating its potential as a dietary supplement for the treatment of hyperlipidemia and obesity.

Schisandra chinensis polysaccharide prevents alcohol-associated liver disease in mice by modulating the gut microbiota-tryptophan metabolism-AHR pathway axis

Polysaccharides are one of the main active components of Schisandra chinensis and have been shown to possess diverse biological activities. In this study, we investigated the preventive effect of Schisandra chinensis polysaccharide (SCP) on alcohol-associated liver disease (ALD) by chronic-plus-binge ethanol feeding and the underlying mechanisms. The results suggest that supplementation with SCP prevents ALD by modulating gut microbiota and tryptophan (Trp) metabolism. SCP significantly enriched intestinal Lactobacillus, especially Lactobacillus reuteri, restored the content of intestinal indole derivatives (TRM, IAA, ILA, IALD) that can activate the aromatic hydrocarbon receptor (AHR), increased the colon AHR pathway activity, repaired intestinal barriers damage, reduced the circulating LPS, and inhibited the liver inflammation, oxidative stress, and lipid accumulation. The in vitro Trp metabolizing capacity was used to selected for a strain of L. reuteri whose in vitro proliferation was similarly promoted by SCP. Importantly, the gavage of the L. reuteri increased intestinal TRM content in mice. In addition, its ALD preventive effects were consistent with SCP and dependent on the colon AHR pathway. Our findings confirm that SCP may prevent ALD by mudulating the gut microbial-Trp metabolism-AHR pathway axis, suggesting that supplementation with the prebiotic SCP is an effective way to prevent ALD.

Thalidomide mitigates Crohn's disease colitis by modulating gut microbiota, metabolites, and regulatory T cell immunity

Thalidomide (THA) is renowned for its potent anti-inflammatory properties. This study aimed to elucidate its underlying mechanisms in the context of Crohn’s disease (CD) development. Mouse colitis models were established by dextran sulfate sodium (DSS) treatment. Fecal microbiota and metabolites were analyzed by metagenomic sequencing and mass spectrometry, respectively. Antibiotic-treated mice served as models for microbiota depletion and transplantation. The expression of Forkhead box P3+ (FOXP3+) Regulatory T cells (Tregs) was measured by flow cytometry and immunohistochemical assay in colitis model and patient cohort. THA inhibited colitis in DSS–treated mice by altering the gut microbiota profile, with an increased abundance of probiotics Bacteroides fragilis (Bf), while pathogenic bacteria were depleted. In addition, THA increased beneficial metabolites bile acids and significantly restored gut barrier function. Transcriptomic profiling revealed that THA inhibited interleukin-17 (IL17), IL1β and cell cycle signaling. Fecal microbiota transplantation from THA-treated mice to microbiota-depleted mice partly recapitulated the effects of THA. Specifically, increased level of gut commensal Bf was observed, correlated with elevated levels of the microbial metabolite 7-Ketolithocholic acid (7-KA) following THA treatment. This microbial metabolite may stable FOXP3 expression by targeting the bile acid receptor farnesol X receptor 1(FXR1) to inhibit autophagy. An interaction between FOXP3 and FXR1 was identified, with binding regions localized to the FOXP3 domain (aa 238-335) and the FXR1 domain (aa 82-222), respectively. Conclusively, THA modulates the gut microbiota and metabolite profiles towards a more beneficial composition, enhances gut barrier function, promotes the differentiation of FOXP3+ Tregs and curbs pro-inflammatory pathways.

Understanding the relationship between breast cancer, immune checkpoint inhibitors, and gut microbiota: a narrative review.

The composition of gut microbiota plays an important role in predicting and influencing outcomes of cancer treated with immunotherapy. Our objective is to summarize the role of gut microbiota and immunotherapy in breast cancer. A systematic search from inception until July 2024 of key search terms including immunity, breast neoplasm, gastrointestinal microbiome/microbiota, fecal microbiota transplantation, pro- and prebiotics, antibiotics and immunotherapy using EMBASE, MEDLINE and CENTRAL was conducted. The results were screened by two reviewers independently and synthesized and presented descriptively. Thirteen studies (5 clinical, 8 pre-clinical) met the eligibility criteria and were published from 2020-2024. Clinical studies showed that the composition and diversity of gut microbiota was associated with patient response to immunotherapy. In pre-clinical studies, dysbiotic states induced by obesity, antibiotics, and diet were associated with immunosuppression and influenced response to programmed cell death-ligand 1 (PD-L1) inhibitors. Microbiota-modulating treatments such as probiotics showed the ability to enhance response to immunotherapy, indicating their potential use as adjunct therapies in breast cancer treatment. The composition of gut microbiota could help predict the chance of response to immunotherapy, and modulating gut microbiota has the potential to enhance the efficacy of chemo-immunotherapy in breast cancer. However, the available data relating to breast cancer are limited. Larger prospective studies are required to further elucidate their role as a biomarker and treatment.

Colon protective effect of Japanese Kampo medicine Daikenchuto by modulating gut microbiota and inducing SLPI

Colon protective effect of Japanese Kampo medicine Daikenchuto by modulating gut microbiota and inducing SLPI

Etiolated-green tea attenuates colonic barrier dysfunction and inflammation in high-fat diet-induced mice by modulating gut microbiota

Colonic barrier dysfunction and inflammation arising from dysbiosis gut microbiota (GM) are strongly associated with a high-fat diet (HFD). Yellow leaf green tea (YLGT), a novel variety of etiolated-green tea, improving the intestinal barrier and inflammation is related to the regulation of GM disorders. To explore the ameliorative mechanism of YLGT, mice were fed an HFD with or without YLGT at doses of 150, 300, and 450 mg kg−1 for 12 weeks. YLGT rectified the GM imbalance, enriched short-chain fatty acid (SCFA)-producing bacteria and gut SCFA contents, activated G protein-coupled receptors, inhibited TLR4/NF-κB signaling pathway, strengthened the tight junction, and repaired the damaged intestinal barrier. The fecal microbiota transplantation experiment further confirmed that the GM was a key element in the anti-obesity and anti-intestinal inflammation effect of YLGT. YLGT has great promise in attenuating obesity-induced intestinal dysfunction. This research provides novel insights into the new mechanism of YLGT on HFD-induced obesity.

Biscuits for the gut: A symphony of FODMAPs and dietary fibre in gut microbiome for irritable bowel syndrome (IBS) management

Emerging evidence suggests gut microbiome alterations significantly influence irritable bowel syndrome (IBS) symptoms with fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs) implicated in triggering symptoms.This study investigated the impact of low and high FODMAP biscuit models on gut microbiota including: Biscuit Flour Control (BiFC), Low-FODMAP Control (LFC), Low-FODMAP High-Fibre Prototype (LFP), and Wholemeal Flour Control (WMC). Biscuits were subjected to in vitro digestion which was followed by in vitro colonic fermentation. 16S rRNA gene sequencing and fatty acid analyses were performed at the end of fermentation.Alpha diversity analysis revealed samples fermented with LFP induced higher diversity compared to samples fermented with BiFC and LFC. The relative abundance of Escherichia-Shigella was significantly lower in LFP fermentates than BiFC fermentates. LEfSe analysis showed LFC fermentates were characterized by higher levels of Citrobacter and Ligilactobacillus. Significantly reduced acetate and butyrate levels were found in LFP fermentates compared to LFC fermentates. WMC fermentates had higher acetate and propionate levels compared to other biscuit fermentates.In conclusion, incorporating low-FODMAP, high-fibre food prototypes may enhance gut microbial diversity and reduce potentially pathogenic bacteria such as Escherichia-Shigella. These findings highlight the potential of personalized dietary interventions, such as the manipulation of biscuit formulations, in modulating gut microbiota and managing IBS symptoms. Industrial relevanceThe low FODMAP diet has been developed as an effective method to moderate the symptoms of IBS patients by reducing bloating and gas in the colon. Our results revealed that the low-FODMAP, high-fibre biscuit model proved more effective than the low-FODMAP biscuit for generating a gut microbiota that could contribute to easing IBS symptoms. Future research should focus on improving this formulation and adapting it to treat the different forms of IBS. This study also demonstrates the efficacy of using colon fermentation models to devise food formulations for gut microbiome-associated diseases.

Analysis of twelve human milk oligosaccharides over fifteen months post-partum in human milk from Chinese mothers

Human milk Oligosaccharides (HMOs) are a major component in human milk and recognized to play an important role in modulating gut microbiota, intestinal cell response, and the development of the brain and immune system. While HMOs levels from Chinese mothers across different regions of China have been reported, data from Hebei are lacking. Twelve HMOs were measured from a cross-section of Hebei Han mothers over a 15-month lactation period. The average total of the 12 measured HMOs was 4872 ± 1902 mg/L, similar to that reported for Han mothers from other Chinese regions. Hebei Han mothers had much lower LNnT (59.0 ± 53.1 mg/L), LNFP II (257.5 ± 211.0 mg/L) and LNFP III (149.9 ± 121.7 mg/L) levels and higher 3FL levels (1875.2 ± 1065.3 mg/L) compared to other regional Chinese mother cohorts. The distribution of secretor and Lewis status for this Hebei mother cohort was measured at 68.5 %, 21.9 %, 8.2 % and 1.4 % respectively for Se+Le+, Se-Le+, Se+Le- and Se-Le- respectively. The results from this study suggest that location has influence over the HMOs concentration.

Xiaobugan decoction prevents CCl4-induced acute liver injury by modulating gut microbiota and hepatic metabolism

BackgroundThe liver plays a crucial role in detoxification and metabolism. When its capacity to metabolize foreign substances is exceeded, it can lead to acute liver injury (ALI). Therefore, preventing liver disease and maintaining daily liver health are of utmost importance. Xiaobugan Decoction (XBGD), a traditional Chinese medicine (TCM) formula, is recorded in ‘Fuxingjue’, is used in folk practice to promote liver health and regulate respiration. However, the hepatoprotective mechanisms of XBGD remained unclear. PurposeWe investigated the prophylactic and hepatoprotective effects of XBGD and explored its related molecular mechanisms using a mouse model of carbon tetrachloride (CCl4)-induced ALI. Study design and methodsXBGD composition was determined using analytical methods, and the main compounds were identified using ultra-high-performance liquid chromatography coupled with Q-Exactive focus mass spectrum (UHPLC-QE-MS) and high-performance liquid chromatography (HPLC). A CCl4-induced L02 cell injury model was employed to explore the protective effects of XBGD on liver cells, and a CCl4-induced ALI mouse model was used to investigate the hepatoprotective effects of XBGD. ResultsCellular experiments demonstrated that XBGD had a protective function against L02 cell damage by increasing cell viability, restoring alanine aminotransferase (ALT), aspartate aminotransferase (AST), and superoxide dismutase (SOD) levels, reducing malondialdehyde (MDA) content, and improving mitochondrial membrane potential (ΔΨm). In the mouse ALI model, XBGD prevented ALI by reducing ALT, AST, and alkaline phosphatase (ALP) levels and inhibiting oxidative stress. Quantitative real-time polymerase chain reaction (qPCR), immumohistochemical staining and western blotting results revealed that XBGD exerted hepatoprotective effects by reducing inflammatory responses and inhibiting cell apoptosis. Furthermore, 1H-NMR metabolomics indicated that XBGD regulates hepatic and intestinal metabolism, whereas 16S rDNA sequencing demonstrated the regulatory effects of XBGD on the gut microbiota. Correlation analysis highlighted the close relationship among gut microbiota, metabolites, and ALI indicators. ConclusionsXBGD is a promising TCM for the prevention of CCl4-induced ALI via regulation of microbiota and metabolism. This study provides a new perspective on the development of hepatoprotective measures and the prevention of liver disease in daily life.

Anemarrhena asphodeloides Bunge polysaccharides alleviate lipoteichoic acid-induced lung inflammation and modulate gut microbiota in mice

Pneumonia remains a prevalent infection primary ailment characterized by severe lung inflammation, leading to respiratory distress and significant mortality rates, particularly affecting young children in less developed regions. This study explores the therapeutic potential of low and high-molecular weight polysaccharides derived from Anemarrhena asphodeloides in a murine model of lipoteichoic acid (LTA)-induced pneumonia, which represents bacterial-induced lung inflammation. Administration of Anemarrhena asphodeloides polysaccharides effectively alleviated LTA-induced symptoms, including decreased lung and colon inflammation, and restored dysbiosis of gut microbiota. Polysaccharide treatment notably increased mucin-2 expression, reduced serum cytokine levels (IL-10, TNF-α), and increased tight junction protein production (ZO-1, Occludin, Claudin). Additionally, polysaccharides promoted a significant recovery in gut microbiota composition, indicating potential prebiotic effects. These findings highlight the therapeutic capability of Anemarrhena asphodeloides polysaccharides against LTA-induced pneumonia through gut microbiota modulation and restored intestinal homeostasis.

Hydroxychloroquine and Sjögren disease: Old friends

About 25–50% of patients with primary Sjögren's syndrome (SjD) take hydroxychloroquine (HCQ). Although it is widely prescribed, and recommended in international guidelines, its use is mostly based on expert opinion and personal experience. Our aim was to provide a comprehensive overview of the pathogenic mechanisms of HCQ, the current clinical evidence for its use, and its safety in primary SjD. HCQ plays an immunomodulatory and anti-inflammatory role, mainly by regulating some interferon proteins, chemokines, BAFF levels, and by modifying gut microbiota. It decreases immunoglobulins and ESR levels. In a Latin-American cohort, the main indications were arthritis, parotid gland enlargement and sicca-only symptoms. In the clinical setting, most studies showing a positive effect of HQC are open trials or retrospective cohorts. Some of these studies may be biased due to the use of non-validated outcomes, and a placebo response effect. To date, only 3 RCTs have investigated the benefits of HCQ, the JOQUER being the pivotal one. This study failed to improve oral/ocular symptoms or ESSDAI score. However, a re-analysis by symptomatology subgroups detected some differences in the ESSPRI. Recently, promising data from a small phase II RCT of the combination of HCQ/leflunomide was reported, but results should be replicated. Currently, the NECESSITY study is investigating treatment combinations that will provide new insights. In the meantime, HCQ plays a central role in the treatment of SjD due to its excellent benefit-risk profile. Data on damage accrual, quality of life, mortality and prevention of cardiovascular risks are also still lacking.

Structural characterization of red yeast rice-derived polysaccharide and its promotion of lipid metabolism and gut function in high-fat diet-induced mice

This study explored the structure and biological activities of a novel polysaccharide, PRY1–1, isolated from red yeast rice (RYR) through solid-state fermentation and biotransformation by Monascus purpureus. The structure of PRY1–1 was characterized by Fourier-transform infrared (FTIR) spectroscopy, nuclear magnetic resonance (NMR) spectroscopy, and other analytical techniques, revealing distinct differences from previously identified mycelial and extracellular polysaccharides. Functional assessments were performed on high-fat diet (HFD)-induced mice to evaluate the impact of PRY1–1 on lipid metabolism and gut function. The results demonstrated that PRY1–1 effectively ameliorated HFD-induced lipid metabolism disorders in the liver and epididymal white adipose tissue (eWAT) by regulating the levels of total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), leptin, adiponectin. Additionally, PRY1–1 protected gut function by enhancing gut barrier integrity, modulating gut microbiota composition, and regulating gut metabolite levels. This study offers new insights into the mechanisms by which RYR polysaccharides influence lipid metabolism, highlighting the potential of PRY1–1 as a functional component with significant health benefits.

Lactiplantibacillus plantarum SG5 inhibits neuroinflammation in MPTP-induced PD mice through GLP-1/PGC-1α pathway

Mounting evidence suggests that alterations in gut microbial composition play an active role in the pathogenesis of Parkinson's disease (PD). Probiotics are believed to modulate gut microbiota, potentially influencing PD development through the microbiota-gut-brain axis. However, the potential beneficial effects of Lactiplantibacillus plantarum SG5 (formerly known as Lactobacillus plantarum, abbreviated as L. plantarum) on PD and its underlying mechanisms remain unclear. In this study, we employed immunofluorescence, Western blotting, ELISA, and 16S rRNA gene sequencing to investigate the neuroprotective effects of L. plantarum SG5 against neuroinflammation in an MPTP-induced PD model and to explore the underlying mechanisms. Our results demonstrated that L. plantarum SG5 ameliorated MPTP-induced motor deficits, dopaminergic neuron loss, and elevated α-synuclein protein levels. Furthermore, SG5 inhibited MPTP-triggered overactivation of microglia and astrocytes in the substantia nigra (SN), attenuated disruption of both blood-brain and intestinal barriers, and suppressed the release of inflammatory factors in the colon and SN. Notably, SG5 modulated the composition and structure of the gut microbiota in mice. The MPTP-induced decrease in colonic GLP-1 secretion was reversed by SG5 treatment, accompanied by increased expression of GLP-1R and PGC-1α in the SN. Importantly, the GLP-1R antagonist Exendin 9–39 and PGC-1α inhibitor SR18292 attenuated the protective effects of SG5 in PD mice. In conclusion, we demonstrate a neuroprotective role of L. plantarum SG5 in the MPTP-induced PD mouse model, which likely involves modulation of the gut microbiota and, significantly, the GLP-1/PGC-1α signaling pathway.

Protective effects of phenylethanol glycosides from Cistanche tubulosa against ALD through modulating gut microbiota homeostasis

Ethnopharmacological relevanceCistanche tubulosa (Schenk) Wight, a Chinese herbal medicine (Rou Cong Rong) with Xinjiang characteristics, was recorded in many medical books in ancient China and often used as a tonic medicine. Supported by the traditional Chinese medicine theory of “homology of liver and kidney,” C. tubulosa (Schenk) Wight has many clinical applications in tonifying the kidney and protecting the liver. Modern pharmacological studies have also found that the protective effects of phenylethanol glycosides from C. tubulosa (Schenk) Wight (CPhGs) play an important role in ameliorating alcoholic liver injury. Aim of the studyWe aimed to investigate whether CPhGs can enhance the therapeutic outcome of alcoholic liver disease (ALD) by targeting the “gut–liver axis,” thus contributing to the knowledge of how Chinese herbs alleviate disease by influencing the gut microbiota. Materials and methodsAn ALD mouse model was established using the Lieber–DeCarli alcohol liquid diet, and the effects of CPhGs on the intestinal barrier and gut microbiota of ALD mice were investigated in a pseudo-sterile mouse model and fecal microbiota transplantation (FMT) mouse model. We fed female C57BL/6N mice with Lieber-DeCarli ethanol liquid diet, according to the NIAAA model. Animal experiment of long-term, ethanol diet intervention for 6W, and short-term for 11d. The FMT experiments were also performed. ResultsCPhGs significantly improved ALD manifestations. ALD mice demonstrated significant gut microbiota dysbiosis and significantly abnormal proliferation of Allobaculum compared with the control diet group in long-term NIAAA mouse model (L-Pair). In mice that received the long-term intervention, the improvement in gut barrier function in the CPhGs-treated group was accompanied by a significant decrease in the abundance of Allobaculum and a significant increase in the abundance of Akkermansia. Furthermore, compared with the mouse were gavaged fecal microbiota from the long-term NIAAA mouse donors (FMT-EtOH), the number of goblet cells, abundance of Akkermansia, and the intestinal short-chain fatty acid concentrations were significantly increased in the mouse were gavaged fecal microbiota from high (700 mg/kg) doses of CPhGs orally in long-term NIAAA model donors (FMT-EtOH-H). Network analysis and species distribution results demonstrated that Akkermansia and Allobaculum were the genera with the highest abundances in the gut microbiota and that their interaction was related to propionic acid metabolism. ConclusionsThe results suggest that CPhGs exert a protective effect against ALD by modulating the abundance and composition of Akkermansia and Allobaculum in the intestine, maintaining the intestinal mucus balance, and safeguarding intestinal barrier integrity.

Edible plant oils modulate gut microbiota during their health-promoting effects: a review.

Edible plant oils are widely used in cooking, cosmetics, health supplement capsules, and other industries, due to their various health-promoting effects. There is increasing evidence that edible plant oils can modulate gut microbiota during their health-promoting effects in animal experiments and cohort or clinical studies. However, the information concerning the gut microbiota modulation of edible plant oils during their health-promoting effects is scattered. In this article, the research progress on gut microbiota modulation of edible plant oils (especially camellia oil, olive oil, and flaxseed oil) is summarized. Meanwhile, a summary on correlations between modulated gut microbiota and changed biochemical indexes is provided. The alterations of edible plant oils on gut microbiota-derived metabolites and the correlations between altered metabolites and modulated gut microbiota as well as changed biochemical indexes are reviewed. Furthermore, the prospects for gut microbiota modulation of edible plant oils during their health-promoting effects are put forward. Existing literature has shown that edible plant oils could modulate gut microbiota during their health-promoting effects, and some differential gut microbiota biomarkers were gained. Some similarities and differences existed while the oils exhibited health-promoting actions. Dosage and treatment time have influences on gut microbiota modulation of edible plant oils. Different edible plant oils exhibited different behaviors in modulating gut microbiota, and edible plant oils were mostly different in modulating gut microbiota compared to edible animal oils. Moreover, the modulated gut microbiota was significantly correlated with the changed biochemical indexes. Furthermore, edible plant oils altered SCFAs and other gut microbiota-derived metabolites. The altered metabolites were obviously correlated with the modulated gut microbiota and changed biochemical indexes. This review is helpful to the future research and application of edible plant oils in health-promoting effects from the perspective of gut microbiota.