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Journal of Endocrinological... Jun 2024People with metabolically healthy (MHO) and metabolically unhealthy obesity (MUO) differ for the presence or absence of cardio-metabolic complications, respectively.
BACKGROUND
People with metabolically healthy (MHO) and metabolically unhealthy obesity (MUO) differ for the presence or absence of cardio-metabolic complications, respectively.
OBJECTIVE
Based on these differences, we are interested in deepening whether these obesity phenotypes could be linked to changes in microbiota and metabolome profiles. In this respect, the overt role of microbiota taxa composition and relative metabolic profiles is not completely understood. At this aim, biochemical and nutritional parameters, fecal microbiota, metabolome and SCFA compositions were inspected in patients with MHO and MUO under a restrictive diet regimen with a daily intake ranging from 800 to 1200 kcal.
METHODS
Blood, fecal samples and food questionnaires were collected from healthy controls (HC), and an obese cohort composed of both MHO and MUO patients. Most impacting biochemical/anthropometric variables from an a priori sample stratification were detected by applying a robust statistics approach useful in lowering the background noise. Bacterial taxa and volatile metabolites were assessed by qPCR and gas chromatography coupled with mass spectrometry, respectively. A targeted GC-MS analyses on SCFAs was also performed.
RESULTS
Instructed to follow a controlled and restricted daily calorie intake, MHO and MUO patients showed differences in metabolic, gut microbial and volatilome signatures. Our data revealed higher quantities of specific pro-inflammatory taxa (i.e., Desulfovibrio and Prevotella genera) and lower quantities of Clostridium coccoides group in MUO subset. Higher abundances in alkane, ketone, aldehyde, and indole VOC classes together with a lower amount of butanoic acid marked the faecal MUO metabolome.
CONCLUSIONS
Compared to MHO, MUO subset symptom picture is featured by specific differences in gut pro-inflammatory taxa and metabolites that could have a role in the progression to metabolically unhealthy status and developing of obesity-related cardiometabolic diseases. The approach is suitable to better explain the crosstalk existing among dysmetabolism-related inflammation, nutrient intake, lifestyle, and gut dysbiosis.
PubMed: 38904913
DOI: 10.1007/s40618-024-02379-2 -
Gualou-Xiebai-Banxia-Tang regulates liver-gut axis to ameliorate Metabolic Syndrome in HFD-fed mice.Phytomedicine : International Journal... Jan 2024Metabolic syndrome (MetS), characterized by obesity, hyperglycemia, and abnormal blood lipid levels, is the pathological basis of many cardiovascular diseases....
BACKGROUND
Metabolic syndrome (MetS), characterized by obesity, hyperglycemia, and abnormal blood lipid levels, is the pathological basis of many cardiovascular diseases. Gualou-Xiebai-Banxia-Tang decoction (GT) was first described in the Synopsis of the Golden Chamber, the earliest traditional Chinese medicine (TCM) monograph on diagnosis and treatment of miscellaneous diseases in China. According to TCM precepts, based on its ability to activate yang to release stagnation, activate qi to reduce depression, remove phlegm, and broaden the chest, GT has been used for more than 2,000 years to treat cardiovascular ailments. However, the molecular bases of its therapeutic mechanisms remain unclear.
PURPOSE
The aim of this study was to identify lipid- and glucose-related hepatic genes differentially regulated by GT, and to assess GT impact on gut microbiota composition, in mice with high-fat diet (HFD)-induced MetS.
STUDY DESIGN AND METHODS
ApoE/ mice were fed with an HFD for 24 weeks, with or without concurrent GT supplementation, to induce MetS. At the study's end, body weight, visceral fat weight, blood lipid levels, and insulin sensitivity were measured, and histopathological staining was used to evaluate hepatosteatosis and intestinal barrier integrity. Liver transcriptomics was used for analysis of differentially expressed genes in liver and prediction of relevant regulatory pathways. Hepatic lipid/glucose metabolism-related genes and proteins were detected by RT-qPCR and western blotting. Gut microbial composition was determined by 16S rRNA gene sequencing.
RESULTS
GT administration reduced MetS-related liver steatosis and weight gain, promoted insulin sensitivity and lipid metabolism, and beneficially modulated gut microbiota composition by decreasing the relative abundance of g_Lachnospiraceae_NK4A136_group and increasing the relative abundance of g_Alistipes. Liver transcriptomics revealed that GT regulated the expression of genes related to lipid and glucose metabolism (Pparγ, Igf1, Gpnmb, and Trem2) and of genes encoding chemokines/chemokine receptors (e.g. Cxcl9 and Cx3cr1). Significant, positive correlations were found for Ccr2, Ccl4, Ccr1, and Cx3cr1 and the g_Lachnospiraceae_NK4A136_group, and between Cxcl9, Ccr2, Ccl4, and Cx3cr1 and g_Desulfovibrio. GT treatment downregulated the protein expressions of SCD1 and CX3CR1 and upregulated the expression of PCK1 protein.
CONCLUSION
GT supplementation alleviates HFD-induced MetS in mice by improving hepatic lipid and glucose metabolism. The anti-metabolic syndrome effects of GT may be related to the regulation of the gut-liver axis.
PubMed: 38901285
DOI: 10.1016/j.phymed.2023.155320 -
PLoS Computational Biology Jun 2024Microbial communities play fundamental roles in every complex ecosystem, such as soil, sea and the human body. The stability and diversity of the microbial community...
Microbial communities play fundamental roles in every complex ecosystem, such as soil, sea and the human body. The stability and diversity of the microbial community depend precisely on the composition of the microbiota. Any change in the composition of these communities affects microbial functions. An important goal of studying the interactions between species is to understand the behavior of microbes and their responses to perturbations. These interactions among species are mediated by the exchange of metabolites within microbial communities. We developed a computational model for the microbial community that has a separate compartment for exchanging metabolites. This model can predict possible metabolites that cause competition, commensalism, and mutual interactions between species within a microbial community. Our constraint-based community metabolic modeling approach provides insights to elucidate the pattern of metabolic interactions for each common metabolite between two microbes. To validate our approach, we used a toy model and a syntrophic co-culture of Desulfovibrio vulgaris and Methanococcus maripaludis, as well as another in co-culture between Geobacter sulfurreducens and Rhodoferax ferrireducens. For a more general evaluation, we applied our algorithm to the honeybee gut microbiome, composed of seven species, and the epiphyte strain Pantoea eucalypti 299R. The epiphyte strain Pe299R has been previously studied and cultured with six different phyllosphere bacteria. Our algorithm successfully predicts metabolites, which imply mutualistic, competitive, or commensal interactions. In contrast to OptCom, MRO, and MICOM algorithms, our COMMA algorithm shows that the potential for competitive interactions between an epiphytic species and Pe299R is not significant. These results are consistent with the experimental measurements of population density and reproductive success of the Pe299R strain.
PubMed: 38900842
DOI: 10.1371/journal.pcbi.1012233 -
Water Research Jun 2024To enhance the performance of the internal circulation (IC) reactor when treating high-sulfate organic wastewater, a laboratory-scale two-phase IC reactor with distinct...
Optimization of sulfate reduction and methanogenesis via phase separation in a two-phase internal circulation reactor for the treatment of high-sulfate organic wastewater.
To enhance the performance of the internal circulation (IC) reactor when treating high-sulfate organic wastewater, a laboratory-scale two-phase IC reactor with distinct phase separation capabilities was designed, and the sulfate reduction and methanogenesis processes were optimized by segregating the reactor into two specialized reaction zones. The results demonstrated that the first and second reaction areas of the two-phase IC reactor could be maintained at 4.5-6.0 and 7.5-8.5, respectively, turning them into the specialized phase for sulfate reduction and methanogenesis. Through phase separation, the two-phase IC reactor achieved a COD degradation and sulfate reduction efficiency of more than 80% when the influent sulfate concentration exceeded 5,000 mg/L, which were 32.32% and 16.04% higher than that before phase separation. Functional analyses indicated a greater activity of both the dissimilatory and assimilatory sulfate reduction pathways in the acidogenic phase, largely due to a rise in the relative abundance of the genera Desulfovibrio, Bacteroides, and Lacticaseibacillus, the primary carriers of sulfate reduction functional genes. In contrast, all the acetoclastic, hydrogenotrophic, and methylotrophic methanogenesis pathways were inhibited in the acidogenic phase but thrived in the methanogenic phase, coinciding with shifts in the genus Methanothrix, which harbors the mcrA, mcrB, and mcrG genes essential for the final transformation step of all three methanogenesis pathways.
PubMed: 38896887
DOI: 10.1016/j.watres.2024.121918 -
Nutrients May 2024An imbalance of energy intake and expenditure is commonly considered as the fundamental cause of obesity. However, individual variations in susceptibility to obesity do...
An imbalance of energy intake and expenditure is commonly considered as the fundamental cause of obesity. However, individual variations in susceptibility to obesity do indeed exist in both humans and animals, even among those with the same living environments and dietary intakes. To further explore the potential influencing factors of these individual variations, male C57BL/6J mice were used for the development of obesity-prone and obesity-resistant mice models and were fed high-fat diets for 16 weeks. Compared to the obesity-prone mice, the obesity-resistant group showed a lower body weight, liver weight, adipose accumulation and pro-inflammatory cytokine levels. 16S rRNA sequencing, which was conducted for fecal microbiota analysis, found that the fecal microbiome's structural composition and biodiversity had changed in the two groups. The genera , , and increased in the obesity-prone mice, and the genera , and were enriched in the obesity-resistant mice. Using widely targeted metabolomics analysis, 166 differential metabolites were found, especially those products involved in arachidonic acid (AA) metabolism, which were significantly reduced in the obesity-resistant mice. Moreover, KEGG pathway analysis exhibited that AA metabolism was the most enriched pathway. Significantly altered bacteria and obesity-related parameters, as well as AA metabolites, exhibited strong correlations. Overall, the phenotypes of the obesity-prone and obesity-resistant mice were linked to gut microbiota and AA metabolism, providing new insight for developing an in-depth understanding of the driving force of obesity resistance and a scientific reference for the targeted prevention and treatment of obesity.
Topics: Animals; Gastrointestinal Microbiome; Diet, High-Fat; Obesity; Male; Mice, Inbred C57BL; Arachidonic Acid; Mice; Feces; RNA, Ribosomal, 16S; Disease Models, Animal; Bacteria; Body Weight
PubMed: 38892512
DOI: 10.3390/nu16111579 -
International Journal of Molecular... Jun 2024Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases in the world, which begins with liver lipid accumulation and is associated with...
Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases in the world, which begins with liver lipid accumulation and is associated with metabolic syndrome. Also, the name chosen to replace NAFLD was metabolic dysfunction-associated steatotic liver disease (MASLD). We performed focused drug screening and found that Cilostazol effectively ameliorated hepatic steatosis and might offer potential for NAFLD treatment. Our aim was to investigate the therapeutic effects of Cilostazol on the glycolipid metabolism and intestinal flora in NAFLD mice and explore the specific mechanism. In this study, 7-week-old male C57BL/6J mice were fed a high-fat diet (HFD) for 8 weeks to induce NAFLD, and then treated with intragastric administration for 12 weeks. The results showed that Cilostazol inhibited liver lipid de novo synthesis by regulating the AMPK-ACC1/SCD1 pathway and inhibited liver gluconeogenesis by the AMPK-PGC1α-G6P/PEPCK pathway. Cilostazol improved the intestinal flora diversity and intestinal microbial composition in the NAFLD mice, and specifically regulated Desulfovibrio and Akkermansia. In addition, Cilostazol increased the level of short-chain fatty acids in the NAFLD mice to a level similar to that in the blank Control group. Cilostazol reduces liver lipid accumulation in NAFLD mice by improving glucose and lipid metabolism disorders and intestinal dysfunction, thereby achieving the purpose of treating NAFLD.
Topics: Animals; Cilostazol; Non-alcoholic Fatty Liver Disease; Mice; Male; Mice, Inbred C57BL; Gastrointestinal Microbiome; Lipid Metabolism; Liver; Diet, High-Fat; Intestinal Diseases; Disease Models, Animal
PubMed: 38892467
DOI: 10.3390/ijms25116280 -
Frontiers in Oncology 2024This study employs a two-sample bidirectional Mendelian randomization (MR) approach to systematically evaluate the causal relationship between gut microbiota and oral...
UNLABELLED
This study employs a two-sample bidirectional Mendelian randomization (MR) approach to systematically evaluate the causal relationship between gut microbiota and oral cavity cancer (OCC).
OBJECTIVE
To address the challenge in establishing the causal relationship between gut microbiota and OCC, we applied a systematic MR analysis.
METHODS
Utilizing GWAS data from the MiBioGen consortium (18,340 individuals) and UK Biobank (n = 264,137), we selected instrumental variables and employed MR-Egger, weighted median, IVW, and weighted mode analyses. Heterogeneity and pleiotropy were assessed using Cochran's Q test and MR-Egger intercept test.
RESULTS
Our findings indicate, at the order level, (OR = 0.9990, 95% CI = 0.9980-1.0000, = ), (OR = 1.0009, 95% CI = 1.0001-1.0018, = ), and (OR = 0.9979, 95% CI = 0.9962-0.9995, = ) exhibit causality on OCC in the Weighted median, IVW, and MR-Egger analyses, respectively. At the family level, (OR = 1.0012, 95% CI = 1.0004-1.0019, = ) and (OR = 0.9970, 95% CI = 0.9948-0.9992, = ) show causality on OCC in IVW and MR-Egger analyses. At the genus level, (IVW, OR = 0.9987, 95% CI = 0.9980-0.9995, = ; MR-Egger, OR = 0.9978, 95% CI = 0.9962-0.9995, = ), (IVW, OR = 1.0008, 95% CI = 1.0001-1.0015, = ), (IVW, OR = 0.9995, 95% CI = 0.9990-1.0000, = ), group (IVW, OR = 1.0005, 95% CI = 1.0000-1.0009, = ), and (IVW, OR = 0.9994, 95% CI = 0.9989-0.9999, = ) are implicated in causing OCC in related analyses.
CONCLUSION
Our study identifies order, family, genus, and group as causally increasing OCC risk. In contrast, order, order, family, genus, genus, and genus are causally associated with a decreased OCC risk. However, further investigations are essential to delineate an optimal gut microbiota composition and unravel the underlying mechanisms of specific bacterial taxa in OCC pathophysiology.
PubMed: 38884080
DOI: 10.3389/fonc.2024.1389678 -
Journal of Dairy Science Jun 2024Inhibition of methyl-coenzyme M reductase can suppress the activity of ruminal methanogens, thereby reducing enteric methane emissions of ruminants. However, developing...
Inhibition of methyl-coenzyme M reductase can suppress the activity of ruminal methanogens, thereby reducing enteric methane emissions of ruminants. However, developing specific and environmentally friendly inhibitors is a challenging endeavor. To identify a natural and effective methane inhibitor that specifically targets methyl-coenzyme M reductase, molecular docking technology was employed to screen a library of phytogenic compounds. A total of 52 candidate compounds were obtained through molecular docking technique. Rosmarinic acid (RA) was one of the compounds that could traverse a narrow channel and bind to the active sites of methyl-coenzyme M reductase, with a calculated binding free energy of -9.355 kcal/mol. Furthermore, the effects of rosmarinic acid supplementation on methane production, rumen fermentation, and the microorganism's community in dairy cows were investigated through in vitro rumen fermentation simulations according to a random design. Supplementation of RA resulted in a 15% decrease in methane production compared with the control. In addition, RA increased the molar proportion of acetate and propionate, whereas the sum of acetate and butyrate divided by propionate was decreased. At the bacterial level, the relative abundance of Rikenellaceae RC9 gut group, Christensenellaceae R7 group, Candidatus Saccharimonas, Desulfovibrio, and Lachnospiraceae FE2018 group decreased with RA supplementation. Conversely, the addition of RA significantly increased the relative abundance of DNF00809 (a genus from Eggerthellaceae), Denitrobacterium, an unclassified genus from Eggerthellaceae, an unclassified genus from Bacteroidales, and an unclassified genus from Atopobiaceae. At the archaeal level, the relative abundance of Methanobrevibacter decreased, while that of Methanosphaera increased with the RA supplementation. These findings suggested that RA has the potential to be used as a novel natural additive for inhibiting ruminal methane production.
PubMed: 38851580
DOI: 10.3168/jds.2024-24970 -
The British Journal of Nutrition Jun 2024The effect of single dietary fiber (DF) on lowering uric acid (UA) level has been reported in the literature. However, the potential protective mechanism of dietary...
The effect of single dietary fiber (DF) on lowering uric acid (UA) level has been reported in the literature. However, the potential protective mechanism of dietary fibre against potassium oxybate-induced hyperuricaemia (HUA), as modelled by prophylactic administration, remains unclear.The data demonstrates that DF significantly decreased serum and cerebral tissue UA concentrations, inhibited xanthine oxidase (XOD) expression and activity in the liver, and reduced levels of creatinine (Cr) and urea nitrogen (BUN) in the serum. Additionally, it mitigated the deposition of amyloid-β (Aβ) in cerebral tissue. Correlation analysis showed that DF modulated the TLR4/NF-κB signaling pathway, attenuating oxidative stress and inflammatory responses in HUA mice. Additionally, DF helps to maintain the composition of the gut microbiota, reducing harmful and enriching beneficial and populations.The results of the faecal metabolomics analysis indicate that DF facilitates the regulation of metabolic pathways involved in oxidative stress and inflammation. These pathways include pyrimidine metabolism, tryptophan metabolism, nucleotide metabolism, and vitamin B6 metabolism. Additionally, the study found that DF has a preventive effect on anxiety-like behaviour induced by HUA. In summary, DF shows promise in mitigating HUA and cognitive deficits, primarily by modulating gut microbiota and metabolites.
PubMed: 38826102
DOI: 10.1017/S0007114524001211 -
Journal of Dairy Science May 2024Oxidative stress is a crucial factor in the age-related decline in physiological, genomic, metabolic, and immunological functions. We screened Lactiplantibacillus...
Oxidative stress is a crucial factor in the age-related decline in physiological, genomic, metabolic, and immunological functions. We screened Lactiplantibacillus plantarum JS19 (L. plantarum JS19), which has been shown to possess therapeutic properties in mice with ulcerative colitis. In this study, L. plantarum JS19-adjunctly fermented goat milk (LAF) was employed to alleviate D-galactose-induced aging and regulate intestinal flora in an aging mouse model. The oral administration of LAF effectively improved the health of spleen and kidney in mice, while mitigating the hepatocyte and oxidative damage induced by D-galactose. Additionally, LAF alleviated D-galactose-induced dysbiosis of the intestinal flora by reducing the abundance of harmful bacteria Desulfovibrio and Helicobacter, while greatly promoting the growth of beneficial Rikenellaceae_RC9_gut_group and Eubacterium. Biomarker 5-hydroxyindole-3-acetic acid was found to be positively linked with those harmful bacteria, while bio-active metabolites were strongly correlated with the beneficial genus. These observations suggest that LAF possesses the capability to mitigate the effects of D-galactose-induced aging in a mouse model through the regulation of oxidative stress, the gut microbiota composition, and levels of fecal metabolites. Consequently, these findings shed light on the potential of LAF as a functional food with anti-aging properties.
PubMed: 38825119
DOI: 10.3168/jds.2024-24733