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Biomedical Journal Jun 2024The incidence of autoimmune diseases is increasing in developed countries, possibly due to the modern Western diet and lifestyle. We showed earlier that polysaccharides...
BACKGROUND
The incidence of autoimmune diseases is increasing in developed countries, possibly due to the modern Western diet and lifestyle. We showed earlier that polysaccharides derived from the medicinal fungus Hirsutella sinensis produced anti-inflammatory, anti-diabetic and anti-obesity effects by modulating the gut microbiota and increasing the abundance of the commensal Parabacteroides goldsteinii in mice fed with a high-fat diet.
METHODS
We examined the effects of the prebiotics, H. sinensis polysaccharides, and probiotic, P. goldsteinii, in a mouse model of imiquimod-induced systemic lupus erythematosus.
RESULTS
The fungal polysaccharides and P. goldsteinii reduced markers of lupus severity, including the increase of spleen weight, proteinuria, and serum levels of anti-DNA auto-antibodies and signal transducer and activator of transcription 4 (STAT4). Moreover, the polysaccharides and P. goldsteinii improved markers of kidney and liver functions such as creatinine, blood urea nitrogen, glomerulus damage and fibrosis, and serum liver enzymes. However, the prebiotics and probiotics did not influence gut microbiota composition, colonic histology, or expression of tight junction proteins in colon tissues.
CONCLUSIONS
Our results indicate that H. sinensis polysaccharides and the probiotic P. goldsteinii can reduce lupus markers in imiquimod-treated mice. These prebiotics and probiotics may therefore be added to other interventions conducive of a healthy lifestyle in order to counter autoimmune diseases.
PubMed: 38901796
DOI: 10.1016/j.bj.2024.100754 -
Food & Function Jun 2024High-fat diets (HFDs) predispose to obesity and liver dysfunctions, and α-dicarbonyl compounds (α-DCs) present in highly processed foods are also implicated in...
High-fat diets (HFDs) predispose to obesity and liver dysfunctions, and α-dicarbonyl compounds (α-DCs) present in highly processed foods are also implicated in relevant pathological processes. However, the synergistic harmful effects of α-DCs co-administered with HFDs remain to be elucidated. In this study, 6-week-old C57BL/6 mice were fed with a HFD co-administered with 0.5% methylglyoxal (MGO)/glyoxal (GO) in water for 8 weeks, and multi-omics approaches were employed to investigate the underlying toxicity mechanisms. The results demonstrated that the MGO intervention with a HFD led to an increased body weight and blood glucose level, accompanied by the biological accumulation of α-DCs and carboxymethyl-lysine, as well as elevated serum levels of inflammatory markers including IL-1β, IL-6, and MIP-1α. Notably, hepatic lesions were observed in the MGO group under HFD conditions, concomitant with elevated levels of malondialdehyde. Transcriptomic analysis revealed enrichment of pathways and differentially expressed genes (DEGs) associated with inflammation and oxidative stress in the liver. Furthermore, α-DC intervention exacerbated gut microbial dysbiosis in the context of a HFD, and through Spearman correlation analysis, the dominant genera such as and in the MGO group and and in the GO group were significantly correlated with a set of DEGs involved in inflammatory and oxidative stress pathways in the liver. This study provides novel insights into the healthy implications of dietary ultra-processed food products in the context of obesity-associated disorders.
PubMed: 38898781
DOI: 10.1039/d3fo05708a -
Bioscience Trends Jun 2024The brain-gut axis intricately links gut microbiota (GM) dysbiosis to the development or worsening of autism spectrum disorder (ASD). However, the precise GM composition...
The brain-gut axis intricately links gut microbiota (GM) dysbiosis to the development or worsening of autism spectrum disorder (ASD). However, the precise GM composition in ASD and the effectiveness of probiotics are unclear. To address this, we performed a thorough meta-analysis of 28 studies spanning PubMed, PsycINFO, Web of Science, Scopus, and MEDLINE, involving 1,256 children with ASD and 1042 neurotypical children, up to February 2024. Using Revman 5.3, we analyzed the relative abundance of 8 phyla and 64 genera. While individuals with ASD did not exhibit significant differences in included phyla, they exhibited elevated levels of Parabacteroides, Anaerostipes, Faecalibacterium, Clostridium, Dorea, Phascolarctobacterium, Lachnoclostridium, Catenibacterium, and Collinsella along with reduced percentages of Barnesiella, Odoribacter, Paraprevotella, Blautia, Turicibacter, Lachnospira, Pseudomonas, Parasutterella, Haemophilus, and Bifidobacterium. Notably, discrepancies in Faecalibacterium, Clostridium, Dorea, Phascolarctobacterium, Catenibacterium, Odoribacter, and Bifidobacterium persisted even upon systematic exclusion of individual studies. Consequently, the GM of individuals with ASD demonstrates an imbalance, with potential increases or decreases in both beneficial and harmful bacteria. Therefore, personalized probiotic interventions tailored to ASD specifics are imperative, rather than a one-size-fits-all approach.
PubMed: 38897955
DOI: 10.5582/bst.2024.01123 -
Nutrients Jun 2024Despite substantial evidence supporting the efficacy of prebiotics for promoting host health and stress resilience, few experiments present evidence documenting the...
Despite substantial evidence supporting the efficacy of prebiotics for promoting host health and stress resilience, few experiments present evidence documenting the dynamic changes in microbial ecology and fecal microbially modified metabolites over time. Furthermore, the literature reports a lack of reproducible effects of prebiotics on specific bacteria and bacterial-modified metabolites. The current experiments examined whether consumption of diets enriched in prebiotics (galactooligosaccharides (GOS) and polydextrose (PDX)), compared to a control diet, would consistently impact the gut microbiome and microbially modified bile acids over time and between two research sites. Male Sprague Dawley rats were fed control or prebiotic diets for several weeks, and their gut microbiomes and metabolomes were examined using 16S rRNA gene sequencing and untargeted LC-MS/MS analysis. Dietary prebiotics altered the beta diversity, relative abundance of bacterial genera, and microbially modified bile acids over time. PICRUSt2 analyses identified four inferred functional metabolic pathways modified by the prebiotic diet. Correlational network analyses between inferred metabolic pathways and microbially modified bile acids revealed deoxycholic acid as a potential network hub. All these reported effects were consistent between the two research sites, supporting the conclusion that dietary prebiotics robustly changed the gut microbial ecosystem. Consistent with our previous work demonstrating that GOS/PDX reduces the negative impacts of stressor exposure, we propose that ingesting a diet enriched in prebiotics facilitates the development of a health-promoting gut microbial ecosystem.
Topics: Animals; Prebiotics; Male; Gastrointestinal Microbiome; Rats, Sprague-Dawley; Oligosaccharides; Glucans; Rats; Bile Acids and Salts; Feces; Bacteria; RNA, Ribosomal, 16S; Diet
PubMed: 38892722
DOI: 10.3390/nu16111790 -
International Journal of Molecular... May 2024The role of the gut microbiota and its interplay with host metabolic health, particularly in the context of type 2 diabetes mellitus (T2DM) management, is garnering... (Comparative Study)
Comparative Study
The role of the gut microbiota and its interplay with host metabolic health, particularly in the context of type 2 diabetes mellitus (T2DM) management, is garnering increasing attention. Dipeptidyl peptidase 4 (DPP4) inhibitors, commonly known as gliptins, constitute a class of drugs extensively used in T2DM treatment. However, their potential interactions with gut microbiota remain poorly understood. In this study, we employed computational methodologies to investigate the binding affinities of various gliptins to DPP4-like homologs produced by intestinal bacteria. The 3D structures of DPP4 homologs from gut microbiota species, including , , , , and sp., were predicted using computational modeling techniques. Subsequently, molecular dynamics simulations were conducted for 200 ns to ensure the stability of the predicted structures. Stable structures were then utilized to predict the binding interactions with known gliptins through molecular docking algorithms. Our results revealed binding similarities of gliptins toward bacterial DPP4 homologs compared to human DPP4. Specifically, certain gliptins exhibited similar binding scores to bacterial DPP4 homologs as they did with human DPP4, suggesting a potential interaction of these drugs with gut microbiota. These findings could help in understanding the interplay between gliptins and gut microbiota DPP4 homologs, considering the intricate relationship between the host metabolism and microbial communities in the gut.
Topics: Dipeptidyl Peptidase 4; Diabetes Mellitus, Type 2; Humans; Dipeptidyl-Peptidase IV Inhibitors; Molecular Dynamics Simulation; Gastrointestinal Microbiome; Molecular Docking Simulation; Protein Binding; Bacteria; Bacterial Proteins; Binding Sites
PubMed: 38891933
DOI: 10.3390/ijms25115744 -
Foods (Basel, Switzerland) May 2024Polysaccharides from have garnered attention for their diverse and well-documented biological activities. In this study, we isolated three ethanol-fractionated...
Polysaccharides from have garnered attention for their diverse and well-documented biological activities. In this study, we isolated three ethanol-fractionated polysaccharides from (EPDO) and investigated their digestive properties and effects on gut microbiota regulation in vitro. The results indicated that after simulating digestion in saliva, gastric, and small intestinal fluids, three EPDOs, EPDO-40, EPDO-60 and EPDO-80, with molecular weights () of 442.6, 268.3 and 50.8 kDa, respectively, could reach the large intestine with a retention rate exceeding 95%. During in vitro fermentation, the EPDOs were broken down in a "melting" manner, resulting in a decrease in their . EPDO-60 degraded more rapidly than EPDO-40, likely due to its moderate . After 24 h, the total production of short-chain fatty acids (SCFAs) for EPDO-60 reached 51.2 ± 1.9 mmol/L, which was higher than that of EPDO-80. Additionally, there was an increase in the relative abundance of , which are capable of metabolizing polysaccharides. EPDO-60 also promoted the growth of specific microbiota, including 9 and , which could potentially benefit from these polysaccharides. Most notably, by comparing the gut microbiota produced by different fermentation carbon sources, we identified the eight most differential gut microbiota specialized in polysaccharide metabolism at the genus level. Functional prediction of these eight differential genera suggested roles in controlling replication and repair, regulating metabolism, and managing genetic information transmission. This provides a new reference for elucidating the specific mechanisms by which EPDOs influence the human body. These findings offer new evidence to explain how EPDOs differ in their digestive properties and contribute to the establishment of a healthy gut microbiota environment in the human body.
PubMed: 38890903
DOI: 10.3390/foods13111675 -
Gut Microbes 2024Alcohol-related liver disease (ALD) is recognized as a global health crisis, contributing to approximately 20% of liver cancer-associated fatalities. Dysbiosis of the...
Alcohol-related liver disease (ALD) is recognized as a global health crisis, contributing to approximately 20% of liver cancer-associated fatalities. Dysbiosis of the gut microbiome is associated with the development of ALD, with the gut microbial metabolite urolithin A (UA) exhibiting a potential for alleviating liver symptoms. However, the protective efficacy of UA against ALD and its underlying mechanism mediated by microbiota remain elusive. In this study, we provide evidence demonstrating that UA effectively ameliorates alcohol-induced metabolic disorders and hepatic endoplasmic reticulum (ER) stress through a specific gut-microbiota-liver axis mediated by major urinary protein 1 (MUP1). Moreover, UA exhibited the potential to restore alcohol-induced dysbiosis of the intestinal microbiota by enriching the abundance of (), (), and (), along with their derived metabolite propionic acid. Partial attenuation of the hepatoprotective effects exerted by UA was observed upon depletion of gut microbiota using antibiotics. Subsequently, a fecal microbiota transplantation (FMT) experiment was conducted to evaluate the microbiota-dependent effects of UA in ALD. FMT derived from mice treated with UA exhibited comparable efficacy to direct UA treatment, as it effectively attenuated ER stress through modulation of MUP1. It was noteworthy that strong associations were observed among the hepatic MUP1, gut microbiome, and metabolome profiles affected by UA. Intriguingly, oral administration of UA-enriched , , and can enhance propionic acid production to effectively suppress ER stress via MUP1, mimicking UA treatment. Collectively, these findings elucidate the causal mechanism that UA alleviated ALD through the gut-microbiota-liver axis. This unique mechanism sheds light on developing novel microbiome-targeted therapeutic strategies against ALD.
Topics: Gastrointestinal Microbiome; Animals; Mice; Liver; Liver Diseases, Alcoholic; Male; Endoplasmic Reticulum Stress; Mice, Inbred C57BL; Coumarins; Dysbiosis; Humans; Bacteria
PubMed: 38889450
DOI: 10.1080/19490976.2024.2367342 -
Journal of Agricultural and Food... Jul 2024Extracellular vesicles released by probiotics have been demonstrated to effectively alleviate intestinal inflammation, yet the precise underlying mechanisms remain...
Extracellular vesicles released by probiotics have been demonstrated to effectively alleviate intestinal inflammation, yet the precise underlying mechanisms remain unclear. In this research, for the first time, UJS001 (LP-UJS) was isolated from fermented sauerkraut in Zhenjiang, China. Thereafter, the therapeutic effect of LP-UJS-derived extracellular vesicles (LP-UJS-EVs) on dextran sulfate sodium-induced ulcerative colitis (UC) in mice was analyzed to elucidate the immune mechanisms. According to our findings, LP-UJS-EVs played a pivotal role in restoring the intestinal barrier and alleviating intestinal inflammation. Notably, LP-UJS-EVs induced M2 polarization of macrophages, promoted the release of IL-10 and TGF-β, inhibited the release of histamine, IL-6, and TNF-α, and exerted regulatory effects on intestinal microflora, as evidenced by the reduced abundances of , , , and , alongside the enhanced abundance of . Furthermore, both LP-UJS and LP-UJS-EVs affected the lysine degradation pathway and significantly increased the abundance of related metabolites, especially oxoadipic acid. In summary, our results underscore the substantial therapeutic potential of LP-UJS and its secreted EVs in the treatment of UC.
Topics: Colitis, Ulcerative; Lactobacillus plantarum; Animals; Mice; Extracellular Vesicles; Macrophages; Gastrointestinal Microbiome; Probiotics; Male; Humans; Mice, Inbred C57BL; Homeostasis; Interleukin-10; Tumor Necrosis Factor-alpha; Dextran Sulfate; Transforming Growth Factor beta
PubMed: 38885172
DOI: 10.1021/acs.jafc.4c01758 -
Journal of Agricultural and Food... Jun 2024d-Pinitol (DP) is primarily found in , which has been shown to have hypoglycemic and protective effects on target organs. However, the mechanism of DP in treating...
d-Pinitol (DP) is primarily found in , which has been shown to have hypoglycemic and protective effects on target organs. However, the mechanism of DP in treating diabetic sarcopenia (DS) is still unclear. To explore the underlying mechanism of DS and the protective targets of DP by high-throughput analysis of 16S rRNA gene, metabolome, and the proteome. Streptozotocin-induced SAMP8 mice were intragastrically administrated DP (150 mg/kg) for 8 weeks. Fecal 16S rRNA gene sequencing and gastrocnemius muscle metabolomic and proteomic analyses were completed to investigate the gut-muscle axis interactions. DP significantly alleviated the muscle atrophy in diabetic mice. Dysfunction of the gut microbiota was observed in the DS mice. DP significantly reduced the Parabacteroides, Akkermansia, and Enterobacteriaceae, while it increased Lachnospiraceae_NK4A136. Metabolome and proteome revealed that 261 metabolites and 626 proteins were significantly changed in the gastrocnemius muscle of diabetic mice. Among these, DP treatment restored 44 metabolites and 17 proteins to normal levels. Functional signaling pathways of DP-treated diabetic mice included nucleotide metabolism, β-alanine, histidine metabolism, ABC transporters, and the calcium signaling pathway. We systematically explored the molecular mechanism of DS and the protective effect of DP, providing new insights that may advance the treatment of sarcopenia.
Topics: Animals; Gastrointestinal Microbiome; Mice; Sarcopenia; Male; Proteome; Metabolome; Inositol; Muscle, Skeletal; Humans; Bacteria
PubMed: 38875577
DOI: 10.1021/acs.jafc.4c03929 -
Scientific Reports Jun 2024Intestinal parasitic infections (IPIs) can lead to significant morbidity and mortality in cancer patients. While they are unlikely to cause severe disease and are...
Intestinal parasitic infections (IPIs) can lead to significant morbidity and mortality in cancer patients. While they are unlikely to cause severe disease and are self-limiting in healthy individuals, cancer patients are especially susceptible to opportunistic parasitic infections. The gut microbiota plays a crucial role in various aspects of health, including immune regulation and metabolic processes. Parasites occupy the same environment as bacteria in the gut. Recent research suggests intestinal parasites can disrupt the normal balance of the gut microbiota. However, there is limited understanding of this co-infection dynamic among cancer patients in Malaysia. A study was conducted to determine the prevalence and relationship between intestinal parasites and gut microbiota composition in cancer patients. Stool samples from 134 cancer patients undergoing active treatment or newly diagnosed were collected and examined for the presence of intestinal parasites and gut microbiota composition. The study also involved 17 healthy individuals for comparison and control. Sequencing with 16S RNA at the V3-V4 region was used to determine the gut microbial composition between infected and non-infected cancer patients and healthy control subjects. The overall prevalence of IPIs among cancer patients was found to be 32.8%. Microsporidia spp. Accounted for the highest percentage at 20.1%, followed by Entamoeba spp. (3.7%), Cryptosporidium spp. (3.0%), Cyclospora spp. (2.2%), and Ascaris lumbricoides (0.8%). None of the health control subjects tested positive for intestinal parasites. The sequencing data analysis revealed that the gut microbiota diversity and composition were significantly different in cancer patients than in healthy controls (p < 0.001). A significant dissimilarity was observed in the bacterial composition between parasite-infected and non-infected patients based on Bray-Curtis (p = 0.041) and Jaccard (p = 0.021) measurements. Bacteria from the genus Enterococcus were enriched in the parasite-infected groups, while Faecalibacterium prausnitzii reduced compared to non-infected and control groups. Further analysis between different IPIs and non-infected individuals demonstrated a noteworthy variation in Entamoeba-infected (unweighted UniFrac: p = 0.008), Cryptosporidium-infected (Bray-Curtis: p = 0.034) and microsporidia-infected (unweighted: p = 0.026; weighted: p = 0.019; Jaccard: p = 0.031) samples. No significant dissimilarity was observed between Cyclospora-infected groups and non-infected groups. Specifically, patients infected with Cryptosporidium and Entamoeba showed increased obligate anaerobic bacteria. Clostridiales were enriched with Entamoeba infections, whereas those from Coriobacteriales decreased. Bacteroidales and Clostridium were found in higher abundance in the gut microbiota with Cryptosporidium infection, while Bacillales decreased. Additionally, bacteria from the genus Enterococcus were enriched in microsporidia-infected patients. In contrast, bacteria from the Clostridiales order, Faecalibacterium, Parabacteroides, Collinsella, Ruminococcus, and Sporosarcina decreased compared to the non-infected groups. These findings underscore the importance of understanding and managing the interactions between intestinal parasites and gut microbiota for improved outcomes in cancer patients.
Topics: Humans; Malaysia; Gastrointestinal Microbiome; Male; Female; Middle Aged; Intestinal Diseases, Parasitic; Adult; Neoplasms; Aged; Feces; Tertiary Care Centers; Hospitals, Teaching; Prevalence; Cryptosporidium; Entamoeba; Microsporidia; Coinfection; RNA, Ribosomal, 16S
PubMed: 38871760
DOI: 10.1038/s41598-024-59969-6