Digesting the complex metabolic effects of diet on the host and microbiome.

The past 50 years of interdisciplinary research in humans and model organisms has delivered unprecedented insights into the mechanisms through which diet affects energy balance. However, translating these results to prevent and treat obesity and its associated diseases remains challenging. Given the vast scope of this literature, we focus this Review on recent conceptual advances in molecular nutrition targeting the management of energy balance, including emerging dietary and pharmaceutical interventions and their interactions with the human gut microbiome. Notably, multiple current dietary patterns of interest embrace moderate-to-high fat intake or prioritize the timing of eating over macronutrient intake. Furthermore, the rapid expansion of microbiome research findings has complicated multiple longstanding tenets of nutrition while also providing new opportunities for intervention. Continued progress promises more precise and reliable dietary recommendations that leverage our growing knowledge of the microbiome, the changing landscape of clinical interventions, and our molecular understanding of human biology.

Gut microbiota metabolite tyramine ameliorates high-fat diet-induced insulin resistance via increased Ca2+ signaling.

The gut microbiota and their metabolites are closely linked to obesity-related diseases, such as type 2 diabetes, but their causal relationship and underlying mechanisms remain largely elusive. Here, we found that dysbiosis-induced tyramine (TA) suppresses high-fat diet (HFD)-mediated insulin resistance in both Drosophila and mice. In Drosophila, HFD increases cytosolic Ca2+ signaling in enterocytes, which, in turn, suppresses intestinal lipid levels. 16 S rRNA sequencing and metabolomics revealed that HFD leads to increased prevalence of tyrosine decarboxylase (Tdc)-expressing bacteria and resulting tyramine production. Tyramine acts on the tyramine receptor, TyrR1, to promote cytosolic Ca2+ signaling and activation of the CRTC-CREB complex to transcriptionally suppress dietary lipid digestion and lipogenesis in enterocytes, while promoting mitochondrial biogenesis. Furthermore, the tyramine-induced cytosolic Ca2+ signaling is sufficient to suppress HFD-induced obesity and insulin resistance in Drosophila. In mice, tyramine intake also improves glucose tolerance and insulin sensitivity under HFD. These results indicate that dysbiosis-induced tyramine suppresses insulin resistance in both flies and mice under HFD, suggesting a potential therapeutic strategy for related metabolic disorders, such as diabetes.

Beneficial metabolic effects of PAHSAs depend on the gut microbiota in diet-induced obese mice but not in chow-fed mice.

Dietary lipids play an essential role in regulating the function of the gut microbiota and gastrointestinal tract, and these luminal interactions contribute to mediating host metabolism. Palmitic Acid Hydroxy Stearic Acids (PAHSAs) are a family of lipids with antidiabetic and anti-inflammatory properties, but whether the gut microbiota contributes to their beneficial effects on host metabolism is unknown. Here, we report that treating chow-fed female and male germ-free (GF) mice with PAHSAs improves glucose tolerance, but these effects are lost upon high fat diet (HFD) feeding. However, transfer of feces from PAHSA-treated, but not vehicle-treated, chow-fed conventional mice increases insulin sensitivity in HFD-fed GF mice. Thus, the gut microbiota is necessary for, and can transmit, the insulin-sensitizing effects of PAHSAs in HFD-fed GF male mice. Analyses of the cecal metagenome and lipidome of PAHSA-treated mice identified multiple lipid species that associate with the gut commensal Bacteroides thetaiotaomicron (Bt) and with insulin sensitivity resulting from PAHSA treatment. Supplementing live, and to some degree, heat-killed Bt to HFD-fed female mice prevented weight gain, reduced adiposity, improved glucose tolerance, fortified the colonic mucus barrier and reduced systemic inflammation compared to HFD-fed controls. These effects were not observed in HFD-fed male mice. Furthermore, ovariectomy partially reversed the beneficial Bt effects on host metabolism, indicating a role for sex hormones in mediating the Bt probiotic effects. Altogether, these studies highlight the fact that PAHSAs can modulate the gut microbiota and that the microbiota is necessary for the beneficial metabolic effects of PAHSAs in HFD-fed mice.

A high-fat diet promotes cancer progression by inducing gut microbiota-mediated leucine production and PMN-MDSC differentiation.

A high-fat diet (HFD) is a high-risk factor for the malignant progression of cancers through the disruption of the intestinal microbiota. However, the role of the HFD-related gut microbiota in cancer development remains unclear. This study found that obesity and obesity-related gut microbiota were associated with poor prognosis and advanced clinicopathological status in female patients with breast cancer. To investigate the impact of HFD-associated gut microbiota on cancer progression, we established various models, including HFD feeding, fecal microbiota transplantation, antibiotic feeding, and bacterial gavage, in tumor-bearing mice. HFD-related microbiota promotes cancer progression by generating polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs). Mechanistically, the HFD microbiota released abundant leucine, which activated the mTORC1 signaling pathway in myeloid progenitors for PMN-MDSC differentiation. Clinically, the elevated leucine level in the peripheral blood induced by the HFD microbiota was correlated with abundant tumoral PMN-MDSC infiltration and poor clinical outcomes in female patients with breast cancer. These findings revealed that the "gut-bone marrow-tumor" axis is involved in HFD-mediated cancer progression and opens a broad avenue for anticancer therapeutic strategies by targeting the aberrant metabolism of the gut microbiota.

Intermittent fasting and high-intensity interval training do not alter gut microbiota composition in adult women with obesity.

Obesity is advancing at an accelerated pace, and yet its treatment is still an emerging field. Although studies have demonstrated the role of the microbiota in the pathogenesis of obesity, this is the first study to show the effects of intermittent fasting (IF), combined or not with exercise, and high-intensity interval training (HIIT) on the gut microbiota composition in women with obesity. Our hypothesis is that IF combined with HIIT can promote the remodeling of the composition and function of the gut microbiota. Thirty-six women with obesity, aged between 18 and 40 yr, participated in the study. They were randomly divided into three groups: 1) IF associated with HIIT group [IF + exercise group (EX), n = 15]; 2) HIIT group (EX, n = 11); and 3) IF group (IF, n = 10). Interventions took place over 8 wk, and all assessments were performed preintervention and postintervention. The HIIT circuit was performed 3 times/wk, for 25 min/session. The IF protocol was a 5:2 (2 times/wk). Multiplex analysis of inflammatory cytokines, sequencing of the 16S rRNA gene, and gas chromatography to measure fecal concentrations of short-chain fatty acids (SCFAs) were performed. This study was registered on ClinicalTrials.gov (NCT05237154). Exercise increased fecal acetate concentrations (P = 0.04), but no changes were observed in the composition and functional profile of the microbiota. The interventions did not change the composition of the microbiota, but exercise may play a modulatory role in the production of acetate. This investigation provides clinical insights into the use of IF and HIIT for women with obesity.NEW & NOTEWORTHY This is the first investigation about alternate-day fasting combined with HITT on the gut microbiota of obese women. The study contributes to the advancement of human science involving IF and HIIT, popular strategies for managing obesity. Previous evidence has explored IF in modulating the microbiota in animal models or specific populations and clinical conditions. Despite the subtle outcomes, this study has relevance and originality in the field of gut microbiota knowledge.

Lactobacillus paracasei subsp. paracasei NTU 101 prevents obesity by regulating AMPK pathways and gut microbiota in obese rat.

This study assessed the anti-obesity effects of Lactobacillus paracasei subsp. paracasei NTU 101 (NTU 101) both in vitro and in vivo. Initially, the cytotoxicity and lipid accumulation inhibitory effects of NTU 101 on 3T3-L1 cells were evaluated using the MTT assay and oil red O assay, respectively. Subsequently, the anti-obesity effects of NTU 101 were investigated in high-fat diet-induced obese rat. Moreover, western blotting was performed to measure the obesity-related protein expression of PPARα, PPARß, PPARγ, C/EBPα, C/EBPß, ATGL, p-p38 MAPK, p-ERK1/2, p-AMPK and CPT-1 in both 3T3-L1 adipocytes and adipose and liver tissues. Treatment with 16 × 108 CFU/mL NTU 101 reduced lipid accumulation in 3T3-L1 adipocytes by more than 50 %. Oral administration of NTU 101 significantly attenuated body weight gain, as well as adipose tissue weight. NTU 101 administration enhanced fatty acid oxidation increasing expression levels of PPARα, CPT-1, and p-AMPK proteins in liver tissue, while simultaneously inhibited adipogenesis by reducing PPARγ and C/EBPα proteins in adipose tissue. Furthermore, NTU 101 supplementation positively modulated the composition of gut microbiota, notably increasing the abundance of Akkermansiaceae. This present study suggests that NTU 101 exerts anti-obesity effects by regulating gut microbiota, fatty acid oxidation, lipolysis and adipogenesis.

Role of the Intestine and Its Gut Microbiota in Metabolic Syndrome and Obesity.

The metabolic syndrome (MetSyn) is currently one of the biggest global health challenges because of its impact on public health. MetSyn includes the cluster of metabolic disorders including obesity, high blood pressure, hyperglycemia, high triglyceride levels, and hepatic steatosis. Together, these abnormalities increase the cardiovascular risk of individuals and pose a threat to healthcare systems worldwide. To better understand and address this complex issue, recent research has been increasingly focusing on unraveling the delicate interplay between metabolic disorders and the intestines and more specifically our gut microbiome. The gut microbiome entails all microorganisms inhabiting the gastrointestinal tract and plays a pivotal role in metabolic processes and overall health of its host. Emerging evidence proves an association between the gut microbiome composition and aspects of MetSyn, such as obesity. Understanding these relationships is crucial because they offer valuable insights into the mechanisms underlying development and progression of metabolic disorders and possible treatment options. Yet, how should we interpret this relationship? This review focuses on the interplay between the gut and MetSyn. In addition, we have reviewed the existing evidence of the gut microbiome and its association with and impact on metabolic disorders, in an attempt to understand the complex interactions and nature of this association. We also explored potential therapeutic options targeting the gut to modify metabolic disorders and obesity.

Characterization of the Small Bowel Microbiome Reveals Different Profiles in Human Subjects Who Are Overweight or Have Obesity.

INTRODUCTION: Gut microbiome changes are linked to obesity, but findings are based on stool data. In this article, we analyzed the duodenal microbiome and serum biomarkers in subjects with normal weight, overweight, and obesity. METHODS: Duodenal aspirates and serum samples were obtained from subjects undergoing standard-of-care esophagogastroduodenoscopy without colon preparation. Aspirate DNAs were analyzed by 16S rRNA and shotgun sequencing. Predicted microbial metabolic functions and serum levels of metabolic and inflammatory biomarkers were also assessed. RESULTS: Subjects with normal weight (N = 105), overweight (N = 67), and obesity (N = 42) were identified. Overweight-specific duodenal microbial features include lower relative abundance (RA) of Bifidobacterium species and Escherichia coli strain K-12 and higher Lactobacillus intestinalis , L. johnsonii , and Prevotella loescheii RA. Obesity-specific features include higher Lactobacillus gasseri RA and lower L. reuteri (subspecies rodentium ), Alloprevotella rava , and Leptotrichia spp RA. Escalation features (progressive changes from normal weight through obesity) include decreasing Bacteroides pyogenes , Staphylococcus hominis , and unknown Faecalibacterium species RA, increasing RA of unknown Lactobacillus and Mycobacterium species, and decreasing microbial potential for biogenic amines metabolism. De-escalation features (direction of change altered in normal to overweight and overweight to obesity) include Lactobacillus acidophilus , L. hominis , L. iners , and Bifidobacterium dentium . An unknown Lactobacillus species is associated with type IIa dyslipidemia and overweight, whereas Alloprevotella rava is associated with type IIb and IV dyslipidemias. DISCUSSION: Direct analysis of the duodenal microbiome has identified key genera associated with overweight and obesity, including some previously identified in stool, e.g., Bifidobacterium and Lactobacillus . Specific species and strains exhibit differing associations with overweight and obesity, including escalation and de-escalation features that may represent targets for future study and therapeutics.

Integrative metagenomic analysis reveals distinct gut microbial signatures related to obesity.

Obesity is a metabolic disorder closely associated with profound alterations in gut microbial composition. However, the dynamics of species composition and functional changes in the gut microbiome in obesity remain to be comprehensively investigated. In this study, we conducted a meta-analysis of metagenomic sequencing data from both obese and non-obese individuals across multiple cohorts, totaling 1351 fecal metagenomes. Our results demonstrate a significant decrease in both the richness and diversity of the gut bacteriome and virome in obese patients. We identified 38 bacterial species including Eubacterium sp. CAG:274, Ruminococcus gnavus, Eubacterium eligens and Akkermansia muciniphila, and 1 archaeal species, Methanobrevibacter smithii, that were significantly altered in obesity. Additionally, we observed altered abundance of five viral families: Mesyanzhinovviridae, Chaseviridae, Salasmaviridae, Drexlerviridae, and Casjensviridae. Functional analysis of the gut microbiome indicated distinct signatures associated to obesity and identified Ruminococcus gnavus as the primary driver for function enrichment in obesity, and Methanobrevibacter smithii, Akkermansia muciniphila, Ruminococcus bicirculans, and Eubacterium siraeum as functional drivers in the healthy control group. Additionally, our results suggest that antibiotic resistance genes and bacterial virulence factors may influence the development of obesity. Finally, we demonstrated that gut vOTUs achieved a diagnostic accuracy with an optimal area under the curve of 0.766 for distinguishing obesity from healthy controls. Our findings offer comprehensive and generalizable insights into the gut bacteriome and virome features associated with obesity, with the potential to guide the development of microbiome-based diagnostics.

Adolescent gut microbiome imbalance and its association with immune response in inflammatory bowel diseases and obesity.

BACKGROUND: Recently, there has been an increase in the number of studies focusing on the association between the gut microbiome and obesity or inflammatory diseases, especially in adults. However, there is a lack of studies investigating the association between gut microbiome and gastrointestinal (GI) diseases in adolescents. METHOD: We obtained 16S rRNA-seq datasets for gut microbiome analysis from 202 adolescents, comprising ulcerative colitis (UC), Crohn's disease (CD), obesity (Ob), and healthy controls (HC). We utilized Quantitative Insights Into Microbial Ecology (QIIME) and Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) to acquire Operational Taxonomic Units (OTUs). Subsequently, we analyzed Kyoto Encyclopedia of Genes and Genomes (KEGG) Orthology (KO) terms and pathway enrichment for the identified OTUs. RESULTS: In this study, we investigated the difference between the gut microbiomes in adolescents with GI diseases and those in healthy adolescents using 202 samples of 16S rRNA sequencing data. The distribution of the six main gut microbiota (i.e., unclassified Dorea, unclassified Lachnospiraceae, unclassified Ruminococcus, Faecalibacterium prausnitzii, Prevotella copri, unclassified Sutterella) was different based on the status of obesity and inflammatory diseases. Dysbiosis was observed within Lachnospiraceae in adolescents with inflammatory diseases (i.e., UC and CD), and in adolescents with obesity within Prevotella and Sutterella. More specifically, our results showed that the relative abundance of Faecalibacterium prausnitzii and unclassified Lachnospiraceae was more than 10% and 8% higher, respectively, in the UC group compared to the CD, Ob, and HC groups. Additionally, the Ob group had over 20% and over 3% higher levels of Prevotella copri and unclassified Sutterella, respectively, compared to the UC, CD, and HC groups. Also, inspecting associations between the six specific microbiota and KO terms, we found that the six microbiota -relating KO terms were associated with NOD-like receptor signaling. These six taxa differences may affect the immune system and inflammatory response by affecting NOD-like receptor signaling in the host during critical adolescence. CONCLUSION: In this study, we discovered that dysbiosis of the microbial community had varying degrees of influence on the inflammatory and immune response pathways in adolescents with inflammatory diseases and obesity.

Interactions between the gut microbiome, associated metabolites and the manifestation and progression of heart failure with preserved ejection fraction in ZSF1 rats.

BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) is associated with systemic inflammation, obesity, metabolic syndrome, and gut microbiome changes. Increased trimethylamine-N-oxide (TMAO) levels are predictive for mortality in HFpEF. The TMAO precursor trimethylamine (TMA) is synthesized by the intestinal microbiome, crosses the intestinal barrier and is metabolized to TMAO by hepatic flavin-containing monooxygenases (FMO). The intricate interactions of microbiome alterations and TMAO in relation to HFpEF manifestation and progression are analyzed here. METHODS: Healthy lean (L-ZSF1, n = 12) and obese ZSF1 rats with HFpEF (O-ZSF1, n = 12) were studied. HFpEF was confirmed by transthoracic echocardiography, invasive hemodynamic measurements, and detection of N-terminal pro-brain natriuretic peptide (NT-proBNP). TMAO, carnitine, symmetric dimethylarginine (SDMA), and amino acids were measured using mass-spectrometry. The intestinal epithelial barrier was analyzed by immunohistochemistry, in-vitro impedance measurements and determination of plasma lipopolysaccharide via ELISA. Hepatic FMO3 quantity was determined by Western blot. The fecal microbiome at the age of 8, 13 and 20 weeks was assessed using 16s rRNA amplicon sequencing. RESULTS: Increased levels of TMAO (+ 54%), carnitine (+ 46%) and the cardiac stress marker NT-proBNP (+ 25%) as well as a pronounced amino acid imbalance were observed in obese rats with HFpEF. SDMA levels in O-ZSF1 were comparable to L-ZSF1, indicating stable kidney function. Anatomy and zonula occludens protein density in the intestinal epithelium remained unchanged, but both impedance measurements and increased levels of LPS indicated an impaired epithelial barrier function. FMO3 was decreased (- 20%) in the enlarged, but histologically normal livers of O-ZSF1. Alpha diversity, as indicated by the Shannon diversity index, was comparable at 8 weeks of age, but decreased by 13 weeks of age, when HFpEF manifests in O-ZSF1. Bray-Curtis dissimilarity (Beta-Diversity) was shown to be effective in differentiating L-ZSF1 from O-ZSF1 at 20 weeks of age. Members of the microbial families Lactobacillaceae, Ruminococcaceae, Erysipelotrichaceae and Lachnospiraceae were significantly differentially abundant in O-ZSF1 and L-ZSF1 rats. CONCLUSIONS: In the ZSF1 HFpEF rat model, increased dietary intake is associated with alterations in gut microbiome composition and bacterial metabolites, an impaired intestinal barrier, and changes in pro-inflammatory and health-predictive metabolic profiles. HFpEF as well as its most common comorbidities obesity and metabolic syndrome and the alterations described here evolve in parallel and are likely to be interrelated and mutually reinforcing. Dietary adaption may have a positive impact on all entities.

Maternal high-fat diet regulates offspring hepatic ABCG5 expression and cholesterol metabolism via the gut microbiota and its derived butyrate.

Maternal high-fat diet intake has profound effects on the long-term health of offspring, predisposing them to a higher susceptibility to obesity and metabolic dysfunction-associated steatotic liver disease. However, the detailed mechanisms underlying the role of a maternal high-fat diet in hepatic lipid accumulation in offspring, especially at the weaning age, remain largely unclear. In this study, female C57BL/6J mice were randomly assigned to either a high-fat diet or a control diet, and lipid metabolism parameters were assessed in male offspring at weaning. Gut microbiota analysis and targeted metabolomics of short-chain fatty acids (SCFAs) in these offspring were further performed. Both in vivo and in vitro studies were conducted to explore the role of butyrate in hepatic cholesterol excretion in the liver and HepG2 cells. Our results showed that maternal high-fat feeding led to obesity and dyslipidemia, and exacerbated hepatic lipid accumulation in the livers of offspring at weaning. We observed significant decreases in the abundance of the Firmicutes phylum and the Allobaculum genus, known as producers of SCFAs, particularly butyrate, in the offspring of dams fed a high-fat diet. Additionally, maternal high-fat diet feeding markedly decreased serum butyrate levels and down-regulated ATP-binding cassette transporters G5 (ABCG5) in the liver, accompanied by decreased phosphorylated AMP-activated protein kinase (AMPK) and histone deacetylase 5 (HADC5) expressions. Subsequent in vitro studies revealed that butyrate could induce ABCG5 activation and alleviate lipid accumulation via the AMPK-pHDAC5 pathway in HepG2 cells. Moreover, knockdown of HDAC5 up-regulated ABCG5 expression and promoted cholesterol excretion in HepG2 cells. In conclusion, our study provides novel insights into how maternal high-fat diet feeding inhibits hepatic cholesterol excretion and down-regulates ABCG5 through the butyrate-AMPK-pHDAC5 pathway in offspring at weaning.

Immunology of gut microbiome and liver in non-alcoholic fatty liver disease (NAFLD): mechanisms, bacteria, and novel therapeutic targets.

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the world. Most important contributors to its development are diet and obesity. Gut microbiome's importance for immune system and inflammatory pathways more widely accepted as an important component in NAFLD and other liver diseases' pathogenesis. In this article we review potential mechanisms of microbiome alteration of local and systemic immune responses leading to NAFLD's development, and how can modulate them for the treatment. Our review mentions different immune system pathways and microorganisms regulating metabolism, liver inflammation and fibrosis. We specifically point out TLR-4 as a potential key immune pathway activated by bacterial lipopolysaccharides producing pro-inflammatory cytokines in NAFLD. Also, we discuss three endotoxin-producing strains (Enterobacter cloacae B29, Escherichia coli PY102, Klebsiella pneumoniae A7) that can promote NAFLD development via TLR4-dependent immune response activation in animal models and how they potentially contribute to disease progression in humans. Additionally, we discuss their other immune and non-immune mechanisms contributing to NAFLD pathogenesis. In the end we point out gut microbiome researches' future perspective in NAFLD as a potential new target for both diagnostic and treatment.

Exploring causal effects of gut microbiota and metabolites on body fat percentage using two-sample Mendelian randomization.

AIM: The relationship between the gut microbiota, metabolites and body fat percentage (BFP) remains unexplored. We systematically assessed the causal relationships between gut microbiota, metabolites and BFP using Mendelian randomization analysis. MATERIALS AND METHODS: Single nucleotide polymorphisms associated with gut microbiota, blood metabolites and BFP were screened via a genome-wide association study enrolling individuals of European descent. Summary data from genome-wide association studies were extracted from the MiBioGen consortium and the UK Biobank. The inverse variance-weighted model was the primary method used to estimate these causal relationships. Sensitivity analyses were performed using pleiotropy, Mendelian randomization-Egger regression, heterogeneity tests and leave-one-out tests. RESULTS: In the aspect of phyla, classes, orders, families and genera, we observed that o_Bifidobacteriales [ß = -0.05; 95% confidence interval (CI): -0.07 to -0.03; false discovery rate (FDR) = 2.76 × 10-3], f_Bifidobacteriaceae (ß = -0.05; 95% CI: -0.07 to -0.07; FDR = 2.76 × 10-3), p_Actinobacteria (ß = -0.06; 95% CI: -0.09 to -0.03; FDR = 6.36 × 10-3), c_Actinobacteria (ß = -0.05; 95% CI: -0.08 to -0.02; FDR = 1.06 × 10-2), g_Bifidobacterium (ß = -0.05; 95% CI: -0.07 to -0.02; FDR = 1.85 × 10-2), g_Ruminiclostridium9 (ß = -0.03; 95% CI: -0.06 to -0.01; FDR = 4.81 × 10-2) were negatively associated with BFP. G_Olsenella (ß = 0.02; 95% CI: 0.01-0.03; FDR = 2.16 × 10-2) was positively associated with BFP. Among the gut microbiotas, f_Bifidobacteriales, o_Bifidobacteriales, c_Actinobacteria and p_Actinobacteria were shown to be significantly associated with BFP in the validated dataset. In the aspect of metabolites, we only observed that valine (ß = 0.77; 95% CI: 0.5-1.04; FDR = 8.65 × 10-6) was associated with BFP. CONCLUSIONS: Multiple gut microbiota and metabolites were strongly associated with an increased BFP. Further studies are required to elucidate the mechanisms underlying this putative causality. In addition, BFP, a key indicator of obesity, suggests that obesity-related interventions can be developed from gut microbiota and metabolite perspectives.

Obesity, abdominal obesity, metabolic obesity phenotypes, and Helicobacter pylori infection: results from NHANES 1999-2000.

BACKGROUND: Recent studies on the association between Helicobacter pylori (H. pylori) infection and obesity have reported conflicting results. Therefore, the purpose of our study was to investigate the association of obesity, abdominal obesity, and metabolic obesity phenotypes with H. pylori infection. METHODS: A cross-sectional study of 1568 participants aged 20 to 85 was conducted using the National Health and Nutrition Examination Survey (NHANES) cycle 1999-2000. Logistic regression models were employed to evaluate the association of general obesity as defined by body mass index (BMI), abdominal obesity as defined by waist circumference (WC) and waist-height ratio (WHtR), and metabolic obesity phenotypes with H. pylori seropositivity. Subgroup analyses stratified by age were conducted to explore age-specific differences in this association. RESULTS: After grouping individuals according to their WHtR, the prevalence rate of WHtR ≥ 0.5 in H. pylori-seropositive participants was significantly higher than that in H. pylori-seronegative participants (79.75 vs. 68.39, P < 0.001). The prevalence of H. pylori seropositivity in non-abdominal obesity and abdominal obesity defined by WHtR was 24.97% and 31.80%, respectively (P < 0.001). In the subgroup analysis, the adjusted association between abdominal obesity, as defined by the WHtR, and H. pylori seropositivity was significant in subjects aged < 50 years (OR = 2.23; 95% CI, 1.24-4.01; P = 0.01) but not in subjects aged ≥ 50 years (OR = 0.84; 95% CI, 0.35-1.99; P = 0.66). Subjects older than 50 years old had an OR (95% CI) for metabolically healthy obesity of 0.04 (0.01-0.35) compared with the control group. H. pylori seropositivity was consistently not associated with obesity as defined by BMI. CONCLUSIONS: Abdominal obesity, as defined by the WHtR, was associated with H. pylori infection in subjects aged ≤ 50 years.

Fermented natto powder alleviates obesity by regulating LXR pathway and gut microbiota in obesity rats.

AIM: This study aimed to investigate the positive effect of natto powder on obese rats fed with a high-fat diet (HFD). METHODS AND RESULTS: Sprague-Dawley rats were fed with a HFD for 8 weeks continuously and gavaged with natto powder, respectively, for 8 weeks starting from the ninth week. The results showed that natto powder significantly reduced the body weight of rats and maintained the balance of cholesterol metabolism in the body by inhibiting the activity of liver X receptors (LXR) target genes, increasing the active expression of cholesterol 7 alpha-hydroxylase, and reducing the active expression of sterol-regulatory element-binding protein and 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR). Furthermore, natto powder increased the relative abundance of potentially beneficial microbiota in gut and decreased the relative abundance of obesity-related harmful bacteria, and also increased the Bacteroidetes/Firmicutes ratio and improved the composition of gut microbiota. CONCLUSIONS: Natto powder maintains the balance of cholesterol metabolism by inhibiting the LXR pathway and regulating the gut microbiota.

Metagenomic and metabolomic analysis showing the adverse risk-benefit trade-off of the ketogenic diet.

BACKGROUND: Ketogenic diets are increasingly popular for addressing obesity, but their impacts on the gut microbiota and metabolome remain unclear. This paper aimed to investigate how a ketogenic diet affects intestinal microorganisms and metabolites in obesity. METHODS: Male mice were provided with one of the following dietary regimens: normal chow, high-fat diet, ketogenic diet, or high-fat diet converted to ketogenic diet. Body weight and fat mass were measured weekly using high-precision electronic balances and minispec body composition analyzers. Metagenomics and non-targeted metabolomics data were used to analyze differences in intestinal contents. RESULTS: Obese mice on the ketogenic diet exhibited notable improvements in weight and body fat. However, these were accompanied by a significant decrease in intestinal microbial diversity, as well as an increase in Firmicutes abundance and a 247% increase in the Firmicutes/Bacteroidetes ratio. The ketogenic diet also altered multiple metabolic pathways in the gut, including glucose, lipid, energy, carbohydrate, amino acid, ketone body, butanoate, and methane pathways, as well as bacterial secretion and colonization pathways. These changes were associated with increased intestinal inflammation and dysbiosis in obese mice. Furthermore, the ketogenic diet enhanced the secretion of bile and the synthesis of aminoglycoside antibiotics in obese mice, which may impair the gut microbiota and be associated with intestinal inflammation and immunity. CONCLUSIONS: The study suggest that the ketogenic diet had an unfavorable risk-benefit trade-off and may compromise metabolic homeostasis in obese mice.

High-fat diet, microbiome-gut-brain axis signaling, and anxiety-like behavior in male rats.

Obesity, associated with the intake of a high-fat diet (HFD), and anxiety are common among those living in modern urban societies. Recent studies suggest a role of microbiome-gut-brain axis signaling, including a role for brain serotonergic systems in the relationship between HFD and anxiety. Evidence suggests the gut microbiome and the serotonergic brain system together may play an important role in this response. Here we conducted a nine-week HFD protocol in male rats, followed by an analysis of the gut microbiome diversity and community composition, brainstem serotonergic gene expression (tph2, htr1a, and slc6a4), and anxiety-related defensive behavioral responses. We show that HFD intake decreased alpha diversity and altered the community composition of the gut microbiome in association with obesity, increased brainstem tph2, htr1a and slc6a4 mRNA expression, including in the caudal part of the dorsomedial dorsal raphe nucleus (cDRD), a subregion previously associated with stress- and anxiety-related behavioral responses, and, finally, increased anxiety-related defensive behavioral responses. The HFD increased the Firmicutes/Bacteroidetes ratio relative to control diet, as well as higher relative abundances of Blautia, and decreases in Prevotella. We found that tph2, htr1a and slc6a4 mRNA expression were increased in subregions of the dorsal raphe nucleus in the HFD, relative to control diet. Specific bacterial taxa were associated with increased serotonergic gene expression in the cDRD. Thus, we propose that HFD-induced obesity is associated with altered microbiome-gut-serotonergic brain axis signaling, leading to increased anxiety-related defensive behavioral responses in rats.

Multivariate Analysis and Correlation Study Shows the Impact of Anthropometric and Demographic Variables on Gut Microbiota in Obese Egyptian Children.

Deciphering the gut microbiome's link to obesity is crucial. Our study characterized the gut microbial community in Egyptian children and investigated the effect of covariates on the gut microbiome, body mass index (BMI), geographical location, gender, and age. We used 16S rRNA sequencing to characterize the gut microbial communities of 49 children. We then evaluated these communities for diversity, potential biomarkers, and functional capacity. Alpha diversity of the non-obese group was higher than that of the obese group (Chao1, P = 0.006 and observed species, P = 0.003). Beta diversity analysis revealed significant variations in the gut microbiome between the two geographical locations, Cairo and Ismailia (unweighted UniFrac, P = 0.03) and between obesity statuses, obese and non-obese (weighted UniFrac, P = 0.034; unweighted UniFrac, P = 0.015). We observed a significantly higher Firmicutes/Bacteroidetes ratio in obese males than in non-obese males (P = 0.004). Interestingly, this difference was not seen in females (P = 0.77). Multivariable association with linear models (MaAsLin2) identified 8 microbial features associated with obesity, 12 associated with non-obesity, and found 29 and 13 features specific to Cairo and Ismailia patients, respectively. It has also shown one microbial feature associated with patients under five years old. MaAsLin2, however, failed to recognize any association between gender and the gut microbiome. Moreover, it could find the most predominant features in groups 2-9 but not in group 1. Another method used in the analysis is the Linear discriminant analysis Effect Size (LEfSe) approach, which effectively identified 19 biomarkers linked to obesity, 9 linked non-obesity, 20 linked to patients residing in Cairo, 14 linked to patients in Ismailia, one linked to males, and 12 linked to females. LEfSe could not, however, detect any prevalent bacteria among children younger or older than five. Future studies should take advantage of such correlations, specifically BMI, to determine the interventions needed for obesity management.

Distribution characteristics of intestinal flora in patients with OSAHS and the relationship between different intestinal flora and sleep disorders, hypoxemia and obesity.

OBJECTIVE: To investigate the distribution characteristics of intestinal flora in patients with obstructive sleep apnoea hypopnea syndrome (OSAHS) of different severities and the relationship between different intestinal flora and sleep structure disorder, hypoxemia and obesity. METHODS: A total of 25 healthy volunteers and 80 patients with OSAHS were enrolled in this study. The control group was healthy, and the experimental group comprised patients with OSAHS. The apnoea-hypopnea index (AHI), minimum saturation of peripheral oxygen (SpO2min), mean saturation of peripheral oxygen, body mass index, maximum apnoea time and other indicators were collected in clinical practice. The patients with OSAHS were divided into 20 mild and 42 moderate OSAHS cases, as well as 18 patients with severe OSAHS according to the AHI classification. Bioinformatics-related statistics were analysed using the QIIME2 software, and clinical data were analysed with the SPSS 22.0 software. RESULTS: The changes in microbial alpha diversity in the intestinal flora of patients with OSAHS showed that richness, diversity and evenness decreased, but the beta diversity did not change significantly. The Thermus Anoxybacillus, Anaerofustis, Blautia, Sediminibacterium, Ralstonia, Pelomonas, Ochrobactrum, Thermus Sediminibacterium, Ralstonia, Coccidia, Cyanobacteria, Anoxic bacilli and Anaerobes were negatively correlated with AHI (r = -0.38, -0.36, -0.35, -0.33, -0.31, -0.29, -0.22, -0.18) and positively correlated with SpO2min (r =0.38, 0.2, 0.25, 0.22, 0.24, 0.11, 0.23, 0.15). CONCLUSION: Some bacteria showed a significant correlation with clinical sleep monitoring data, which provides a possibility for the assessment of disease risk, but the mechanisms of their actions in the intestinal tract are not clear at present. Further research and observations are needed.