Decreased circulating IPA levels identify subjects with metabolic comorbidities: A multi-omics study.

In recent years several experimental observations demonstrated that the gut microbiome plays a role in regulating positively or negatively metabolic homeostasis. Indole-3-propionic acid (IPA), a Tryptophan catabolic product mainly produced by C. Sporogenes, has been recently shown to exert either favorable or unfavorable effects in the context of metabolic and cardiovascular diseases. We performed a study to delineate clinical and multiomics characteristics of human subjects characterized by low and high IPA levels. Subjects with low IPA blood levels showed insulin resistance, overweight, low-grade inflammation, and features of metabolic syndrome compared to those with high IPA. Metabolomics analysis revealed that IPA was negatively correlated with leucine, isoleucine, and valine metabolism. Transcriptomics analysis in colon tissue revealed the enrichment of several signaling, regulatory, and metabolic processes. Metagenomics revealed several OTU of ruminococcus, alistipes, blautia, butyrivibrio and akkermansia were significantly enriched in highIPA group while in lowIPA group Escherichia-Shigella, megasphera, and Desulfovibrio genus were more abundant. Next, we tested the hypothesis that treatment with IPA in a mouse model may recapitulate the observations of human subjects, at least in part. We found that a short treatment with IPA (4 days at 20/mg/kg) improved glucose tolerance and Akt phosphorylation in the skeletal muscle level, while regulating blood BCAA levels and gene expression in colon tissue, all consistent with results observed in human subjects stratified for IPA levels. Our results suggest that treatment with IPA may be considered a potential strategy to improve insulin resistance in subjects with dysbiosis.

Prebiotics, probiotics, synbiotics and postbiotics to adolescents in metabolic syndrome.

The prevalence of childhood and adolescent obesity has globally reached alarming dimensions and many adolescents affected by obesity already present one or more obesity-related comorbidities. In recent years, emerging evidence supporting the role of gut microbiota in the pathophysiology of metabolic diseases has been reported and the use of prebiotics, probiotics, synbiotics and postbiotics as a strategy to manipulate gut microbiota has become popular. The aim of this review is to explore the relationship between gut microbiota and metabolic syndrome in adolescents and to discuss the potential use of prebiotics, probiotics, synbiotics and postbiotics for the prevention and treatment of this clinical picture in adolescence. According to the most recent literature, prebiotics, probiotics and synbiotics have no clear effect on MetS, but a possible modulation of anthropometric parameters has been observed after synbiotic supplementation. Only one study has examined the role of postbiotics in alleviating metabolic complications in children with obesity but not in adolescents. More extensive research is needed to support the conclusions drawn so far and to develop effective microbiome-based interventions that may help improving the quality of life of children and adolescents exposed to the increasing prevalence of MetS.

Recipient microbiome-related features predicting metabolic improvement following fecal microbiota transplantation in adults with severe obesity and metabolic syndrome: a secondary analysis of a phase 2 clinical trial.

Microbial-based therapeutics in clinical practice are of considerable interest, and a recent study demonstrated fecal microbial transplantation (FMT) followed by dietary fiber supplements improved glucose homeostasis. Previous evidence suggests that donor and recipient compatibility and FMT protocol are key determinants, but little is known about the involvement of specific recipient factors. Using data from our recent randomized placebo-control phase 2 clinical trial in adults with obesity and metabolic syndrome, we grouped participants that received FMT from one of 4 donors with either fiber supplement into HOMA-IR responders (n = 21) and HOMA-IR non-responders (n = 8). We further assessed plasma bile acids using targeted metabolomics and performed subgroup analyzes to evaluate the effects of recipient parameters and gastrointestinal factors on microbiota engraftment and homeostatic model assessment of insulin resistance (HOMA2-IR) response. The baseline fecal microbiota composition at genus level of recipients could predict the improvements in HOMA2-IR at week 6 (ROC-AUC = 0.70). Prevotella was identified as an important predictor, with responders having significantly lower relative abundance than non-responders (p = .02). In addition, recipients displayed a highly individualized degree of microbial engraftment from donors. Compared to the non-responders, the responders had significantly increased bacterial richness (Chao1) after FMT and a more consistent engraftment of donor-specific bacteria ASVs (amplicon sequence variants) such as Faecalibacillus intestinalis (ASV44), Roseburia spp. (ASV103), and Christensenellaceae spp. (ASV140) (p < .05). Microbiota engraftment was strongly associated with recipients' factors at baseline including initial gut microbial diversity, fiber and nutrient intakes, inflammatory markers, and bile acid derivative levels. This study identified that responders to FMT therapy had a higher engraftment rate in the transplantation of specific donor-specific microbes, which were strongly correlated with insulin sensitivity improvements. Further, the recipient baseline gut microbiota and related factors were identified as the determinants for responsiveness to FMT and fiber supplementation. The findings provide a basis for the development of precision microbial therapeutics for the treatment of metabolic syndrome.

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.

Multi-omics approach to socioeconomic disparity in metabolic syndrome reveals roles of diet and microbiome.

The epidemy of metabolic syndrome (MetS) is typically preceded by adoption of a "risky" lifestyle (e.g., dietary habit) among populations. Evidence shows that those with low socioeconomic status (SES) are at an increased risk for MetS. To investigate this, we recruited 123 obese subjects (body mass index [BMI] ≥ 30) from Chicago. Multi-omic data were collected to interrogate fecal microbiota, systemic markers of inflammation and immune activation, plasma metabolites, and plasma glycans. Intestinal permeability was measured using the sugar permeability testing. Our results suggest a heterogenous metabolic dysregulation among obese populations who are at risk of MetS. Systemic inflammation, linked to poor diet, intestinal microbiome dysbiosis, and gut barrier dysfunction may explain the development of MetS in these individuals. Our analysis revealed 37 key features associated with increased numbers of MetS features. These features were used to construct a composite metabolic-inflammatory (MI) score that was able to predict progression of MetS among at-risk individuals. The MI score was correlated with several markers of poor diet quality as well as lower levels of gut microbial diversity and abnormalities in several species of bacteria. This study reveals novel targets to reduce the burden of MetS and suggests access to healthy food options as a practical intervention.

The number of metabolic syndrome risk factors predicts alterations in gut microbiota in Chinese children from the Huantai study.

BACKGROUND: Evidence on the effect of gut microbiota on the number of metabolic syndrome (MetS) risk factors among children is scarce. We aimed to examine the alterations of gut microbiota with different numbers of MetS risk factors among children. METHODS: Data were collected from a nested case-control study at the baseline of the Huantai Childhood Cardiovascular Health Cohort Study in Zibo, China. We compared the differences in gut microbiota based on 16S rRNA gene sequencing among 72 children with different numbers of MetS risk factors matched by age and sex (i.e., none, one, and two-or-more MetS risk factors; 24 children for each group). RESULTS: The community richness (i.e., the total number of species in the community) and diversity (i.e., the richness and evenness of species in the community) of gut microbiota decreased with an increased number of MetS risk factors in children (P for trend < 0.05). Among genera with a relative abundance greater than 0.01%, the relative abundance of Lachnoclostridium (PFDR = 0.009) increased in the MetS risk groups, whereas Alistipes (PFDR < 0.001) and Lachnospiraceae_NK4A136_group (PFDR = 0.043) decreased in the MetS risk groups compared to the non-risk group. The genus Christensenellaceae_R-7_group excelled at distinguishing one and two-or-more risk groups from the non-risk group (area under the ROC curve [AUC]: 0.84 - 0.92), while the genera Family_XIII_AD3011_group (AUC: 0.73 - 0.91) and Lachnoclostridium (AUC: 0.77 - 0.80) performed moderate abilities in identifying none, one, and two-or-more MetS risk factors in children. CONCLUSIONS: Based on the nested case-control study and the 16S rRNA gene sequencing technology, we found that dysbiosis of gut microbiota, particularly for the genera Christensenellaceae_R-7_group, Family_XIII_AD3011_group, and Lachnoclostridium may contribute to the early detection and the accumulation of MetS risk factors in childhood.

Changes in the Mucosa-Associated Microbiome and Transcriptome across Gut Segments Are Associated with Obesity in a Metabolic Syndrome Porcine Model.

Several studies have suggested a role for gut mucosa-associated microbiota in the development of obesity, but the mechanisms involved are poorly defined. Here, the impact of the gut mucosa-associated microbiota on obesity and related metabolic disorders was evaluated in a metabolic syndrome (MetS) porcine model. Body composition was determined among male Wuzhishan minipigs consuming a high-energy diet (HED) and compared to that of those consuming a normal diet (ND), and gut segments (duodenum, jejunum, ileum, cecum, colon, and rectum) were sampled for paired analysis of mucosa-associated microbiota and transcriptome signatures with 16S rRNA gene and RNA sequencing, respectively. Our data indicated that long-term HED feeding significantly increased body weight and visceral fat deposition and aggravated metabolic disorders. Specially, HED feeding induced mucosa-associated microbiota dysbiosis and selectively increased the abundance of the families Enterobacteriaceae, Moraxellaceae, and Lachnospiraceae in the upper intestine. The association analysis indicated that specific bacteria play key roles in adiposity, e.g., Lactobacillus johnsonii in the duodenum, Actinobacillus indolicus in the jejunum, Acinetobacter johnsonii in the ileum, Clostridium butyricum in the cecum, Haemophilus parasuis in the colon, and bacterium NLAEzlP808, Halomonas taeheungii, and Shewanella sp. JNUH029 in the rectum. Transcriptome data further revealed intestinal lipid metabolism and immune dysfunction in the MetS individuals, which may be associated with obesity and related metabolic disorders. Our results indicated that gut mucosa-associated microbiota dysbiosis has the potential to exacerbate obesity, partially through modulating systemic inflammatory responses. IMPORTANCE Obesity is a major risk factor for metabolic syndrome, which is the most common cause of death worldwide, especially in developed countries. The link between obesity and gut mucosa-associated microbiota is unclear due to challenges associated with the collection of intestinal samples from humans. The current report provides the first insight into obesity-microbiome-gut immunity connections in a metabolic syndrome (MetS) porcine model. The present results show that dysbiosis of mucosal microbiota along the entire digestive tract play a critical role in the proinflammatory response in the host-microbial metabolism axis, resulting in obesity and related metabolic disorders in the MetS model.

Species- and strain-level assessment using rrn long-amplicons suggests donor's influence on gut microbial transference via fecal transplants in metabolic syndrome subjects.

Fecal microbiota transplantation (FMT) is currently used for treating Clostridium difficile infection and explored for other clinical applications in experimental trials. However, the effectiveness of this therapy could vary, and partly depend on the donor's bacterial species engraftment, whose evaluation is challenging because there are no cost-effective strategies for accurately tracking the microbe transference. In this regard, the precise identification of bacterial species inhabiting the human gut is essential to define their role in human health unambiguously. We used Nanopore-based device to sequence bacterial rrn operons (16S-ITS-23S) and to reveal species-level abundance changes in the human gut microbiota of a FMT trial. By assessing the donor and recipient microbiota before and after FMT, we further evaluated whether this molecular approach reveals strain-level genetic variation to demonstrate microbe transfer and engraftment. Strict control over sequencing data quality and major microbiota covariates was critical for accurately estimating the changes in gut microbial species abundance in the recipients after FMT. We detected strain-level variation via single-nucleotide variants (SNVs) at rrn regions in a species-specific manner. We showed that it was possible to explore successfully the donor-bacterial strain (e.g., Parabacteroides merdae) engraftment in recipients of the FMT by assessing the nucleotide frequencies at rrn-associated SNVs. Our findings indicate that the engraftment of donors' microbiota is to some extent correlated with the improvement of metabolic health in recipients and that parameters such as the baseline gut microbiota configuration, sex, and age of donors should be considered to ensure the success of FMT in humans. The study was prospectively registered at the Dutch Trial registry - NTR4488 (https://www.trialregister.nl/trial/4488).

Gut microbiota from Mexican patients with metabolic syndrome and HIV infection: An inflammatory profile.

AIM: A remarkable increase in metabolic syndrome (MetS) has occurred in HIV-infected subjects. Gut dysbiosis is involved in the pathogenesis of metabolic disorders. Therefore, the aim is to explore the profile of the gut microbiota in Mexican population with HIV infection and MetS. METHODS AND RESULTS: In all, 30 HIV-infected patients with MetS were compared to a group of 30 patients without MetS, treated with integrase inhibitors and undetectable viral load were included in the study. Stool samples were analysed by 16S rRNA next-generation sequencing. High-sensitivity C-reactive protein >3 mg L-1 and higher scores in cardiometabolic indices were associated with MetS. The group with MetS was characterized by a decrease in α-diversity, higher abundance of Enterobacteriaceae and Prevotella, as well as a dramatic decrease in bacteria producing short-chain fatty acids. Prevotella negatively correlated with Akkermansia, Lactobacillus and Anaerostipes. Interestingly, the group without MetS presented higher abundance of Faecalibacterium, Ruminococcus, Anaerofilum, Oscillospira and Anaerostipes. Functional pathways related to energy metabolism and inflammation were increased in the group with MetS. CONCLUSIONS: HIV-infected patients with MetS present a strong inflammatory microbiota profile; therefore, future strategies to balance intestinal dysbiosis should be implemented.

Examining the Interaction of the Gut Microbiome with Host Metabolism and Cardiometabolic Health in Metabolic Syndrome.

(1) Background: The microbiota-host cross-talk has been previously investigated, while its role in health is not yet clear. This study aimed to unravel the network of microbial-host interactions and correlate it with cardiometabolic risk factors. (2) Methods: A total of 47 adults with overweight/obesity and metabolic syndrome from the METADIET study were included in this cross-sectional analysis. Microbiota composition (151 genera) was assessed by 16S rRNA sequencing, fecal (m = 203) and plasma (m = 373) metabolites were profiled. An unsupervised sparse generalized canonical correlation analysis was used to construct a network of microbiota-metabolite interactions. A multi-omics score was derived for each cluster of the network and associated with cardiometabolic risk factors. (3) Results: Five multi-omics clusters were identified. Thirty-one fecal metabolites formed these clusters and were correlated with plasma sphingomyelins, lysophospholipids and medium to long-chain acylcarnitines. Seven genera from Ruminococcaceae and a member from the Desulfovibrionaceae family were correlated with fecal and plasma metabolites. Positive correlations were found between the multi-omics scores from two clusters with cholesterol and triglycerides levels. (4) Conclusions: We identified a correlated network between specific microbial genera and fecal/plasma metabolites in an adult population with metabolic syndrome, suggesting an interplay between gut microbiota and host lipid metabolism on cardiometabolic health.

Effects of fecal microbiota transplant on DNA methylation in subjects with metabolic syndrome.

Accumulating evidence shows that microbes with their theater of activity residing within the human intestinal tract (i.e., the gut microbiome) influence host metabolism. Some of the strongest results come from recent fecal microbial transplant (FMT) studies that relate changes in intestinal microbiota to various markers of metabolism as well as the pathophysiology of insulin resistance. Despite these developments, there is still a limited understanding of the multitude of effects associated with FMT on the general physiology of the host, beyond changes in gut microbiome composition. We examined the effect of either allogenic (lean donor) or autologous FMTs on the gut microbiome, plasma metabolome, and epigenomic (DNA methylation) reprogramming in peripheral blood mononuclear cells in individuals with metabolic syndrome measured at baseline (pre-FMT) and after 6 weeks (post-FMT). Insulin sensitivity was determined with a stable isotope-based 2 step hyperinsulinemic clamp and multivariate machine learning methodology was used to uncover discriminative microbes, metabolites, and DNA methylation loci. A larger gut microbiota shift was associated with an allogenic than with autologous FMT. Furthemore, the data results of the the allogenic FMT group data indicates that the introduction of new species can potentially modulate the plasma metabolome and (as a result) the epigenome. Most notably, the introduction of Prevotella ASVs directly correlated with methylation of AFAP1, a gene involved in mitochondrial function, insulin sensitivity, and peripheral insulin resistance (Rd, rate of glucose disappearance). FMT was found to have notable effects on the gut microbiome but also on the host plasma metabolome and the epigenome of immune cells providing new avenues of inquiry in the context of metabolic syndrome treatment for the manipulation of host physiology to achieve improved insulin sensitivity.

Gut microbiota associations with metabolic syndrome and relevance of its study in pediatric subjects.

Childhood obesity and T2DM have shown a recent alarming increase due to important changes in global lifestyle and dietary habits, highlighting the need for urgent and novel solutions to improve global public health. Gut microbiota has been shown to be relevant in human health and its dysbiosis has been associated with MetS, a health condition linked to the onset of relevant diseases including T2DM. Even though there have been recent improvements in the understanding of gut microbiota-host interactions, pediatric gut microbiota has been poorly studied compared to adults. This review provides an overview of MetS and its relevance in school-age children, discusses gut microbiota and its possible association with this metabolic condition including relevant emerging gut microbiome-based interventions for its prevention and treatment, and outlines future challenges and perspectives in preventing microbiota dysbiosis from the early stages of life.

Low-molecular alginate improved diet-induced obesity and metabolic syndrome through modulating the gut microbiota in BALB/c mice.

Alginate is the most abundant polysaccharide in brown seaweed, which is widely used as a food additive, but its high viscosity and gel property limit its applications in foods as a functional ingredient. In this study, low-molecular alginate from Laminaria japonica (L-LJA) was prepared, and its effect on obesity and metabolic syndrome was analyzed in high-fat diet (HFD)-fed mice. L-LJA reduced weight gain, fat accumulation in the liver and epididymal adipose tissue, lipid abnormality and inflammation in HFD-fed mice accompanied with the improvement of gut microbiota. L-LJA modulated the structure of gut microbiota, increased some Bacteroidales members, and reduced some Clostridiales members in mice, which were positively correlated with the improvement of physiological status. Fecal transplant from L-LJA-fed mice reduced fat accumulation in body tissues and lipid abnormality in the serum and liver and increased short chain fatty acids production in HFD-fed mice, confirming that L-LJA-induced gut microbiota alteration played an important role in its bioactivity. L-LJA has better solubility and can be utilized in food systems in high dose, implying that it can be developed as a prebiotic agent to increase both economic value and nutritive value of alginate.

Effects of probiotic supplementation on anthropometric and metabolic characteristics in adults with metabolic syndrome: A systematic review and meta-analysis of randomized clinical trials.

AIMS: We conducted a systematic review and meta-analysis to evaluate evidence from randomized controlled trials (RCTs) documenting the effectiveness of supplementation with pro-/synbiotics versus placebo controls on anthropometric and metabolic (glucoregulatory status, lipid profile) indices in adults with metabolic syndrome (MetS). METHODS: Databases of MEDLINE, Scopus, Embase, Web of Science, and Cochrane Library were searched through March 2020 to identify eligible RCTs evaluating the effects of pro-/synbiotic consumption in adults (≥18 years) with MetS. Mean differences (MDs) and 95% confidence intervals (CIs) were pooled using random-effects models. RESULTS: Ten eligible publications (9 RCTs, n = 344 participants) were included. Supplementation with pro-/synbiotics reduced total cholesterol (TC) in adults with MetS versus placebo (MD: -6.66 mg/dL, 95% CI: -13.25 to -0.07, P = 0.04, I2 = 28.8%, n = 7), without affecting weight, body mass index, waist circumference, fasting blood sugar, homeostasis model assessment for insulin resistance, insulin, triglyceride, low-density lipoprotein cholesterol, or high-density lipoprotein cholesterol (P > 0.05). CONCLUSIONS: Pro-/synbiotic consumption may be beneficial in reducing TC levels in adults with MetS. However, our observations do not support the effectiveness of pro-/synbiotics consumption on other anthropometric or metabolic outcomes of MetS. Further investigations with larger sample sizes are required to confirm these findings.

Gut Microbiota Composition is Associated with Responses to Peanut Intervention in Multiple Parameters Among Adults with Metabolic Syndrome Risk.

INTRODUCTION: Peanuts are widely consumed as a meal ingredient and a snack, and are commonly considered as a healthy food based on their nutrient profile. Peanut consumption has been associated with a lower risk of metabolic syndrome (MetS) in epidemiological studies. This study aims to investigate whether consuming peanuts affects the gut microbiota in adults with risk of MetS and whether the intervention effect of peanuts is associated with gut microbiota composition. METHODS AND RESULTS: This study analyzes the gut microbiota of subjects from a 12-week randomized clinical trial comparing consumption of either peanuts or isocaloric carbohydrate bars. It is observed that there is high inter-individual variability on multiple clinical and anthropometrical parameters in response to peanut consumption. Meanwhile, the gut microbiota composition is also highly person-specific and have minor changes when compared laterally or longitudinally. This study employs a machine-learning algorithm and establishes prediction models using the microbiome data and the responsiveness data of different parameters in subjects with peanut intervention. As a result, it is found that the improvement of MetS risk and numerous parameters, including diastolic blood pressure, body weight, waist circumference, and fasting blood glucose level can be predicted for responsiveness with high accuracy that has a value of area under curve over 0.70 by receiver operating characteristic analysis. CONCLUSION: Together, the findings of this study suggest that individual gut microbiota configuration may modulate host metabolism and alter an individual's response to peanut intervention, thus highlighting the importance of personalized nutrition.

Effects of a Diet Based on Foods from Symbiotic Agriculture on the Gut Microbiota of Subjects at Risk for Metabolic Syndrome.

Diet is a major driver of gut microbiota variation and plays a role in metabolic disorders, including metabolic syndrome (MS). Mycorrhized foods from symbiotic agriculture (SA) exhibit improved nutritional properties, but potential benefits have never been investigated in humans. We conducted a pilot interventional study on 60 adults with ≥ 1 risk factors for MS, of whom 33 consumed SA-derived fresh foods and 27 received probiotics over 30 days, with a 15-day follow-up. Stool, urine and blood were collected over time to explore changes in gut microbiota, metabolome, and biochemical, inflammatory and immunologic parameters; previous dietary habits were investigated through a validated food-frequency questionnaire. The baseline microbiota showed alterations typical of metabolic disorders, mainly an increase in Coriobacteriaceae and a decrease in health-associated taxa, which were partly reversed after the SA-based diet. Improvements were observed in metabolome, MS presence (two out of six subjects no longer had MS) or components. Changes were more pronounced with less healthy baseline diets. Probiotics had a marginal, not entirely favorable, effect, although one out of three subjects no longer suffered from MS. These findings suggest that improved dietary patterns can modulate the host microbiota and metabolome, counteracting the risk of developing MS.

Brown Seaweed Sargassum siliquosum as an Intervention for Diet-Induced Obesity in Male Wistar Rats.

The therapeutic potential of Sargassum siliquosum grown in Australian tropical waters was tested in a rat model of metabolic syndrome. Forty-eight male Wistar rats were divided into four groups of 12 rats and each group was fed a different diet for 16 weeks: corn starch diet (C); high-carbohydrate, high-fat diet (H) containing fructose, sucrose, saturated and trans fats; and C or H diets with 5% S. siliquosum mixed into the food from weeks 9 to 16 (CS and HS). Obesity, hypertension, dyslipidaemia, impaired glucose tolerance, fatty liver and left ventricular fibrosis developed in H rats. In HS rats, S. siliquosum decreased body weight (H, 547 ± 14; HS, 490 ± 16 g), fat mass (H, 248 ± 27; HS, 193 ± 19 g), abdominal fat deposition and liver fat vacuole size but did not reverse cardiovascular and liver effects. H rats showed marked changes in gut microbiota compared to C rats, while S. siliquosum supplementation increased gut microbiota belonging to the family Muribaculaceae. This selective increase in gut microbiota likely complements the prebiotic actions of the alginates. Thus, S. siliquosum may be a useful dietary additive to decrease abdominal and liver fat deposition.

Fecal Metaproteomics Reveals Reduced Gut Inflammation and Changed Microbial Metabolism Following Lifestyle-Induced Weight Loss.

Gut microbiota-mediated inflammation promotes obesity-associated low-grade inflammation, which represents a hallmark of metabolic syndrome. To investigate if lifestyle-induced weight loss (WL) may modulate the gut microbiome composition and its interaction with the host on a functional level, we analyzed the fecal metaproteome of 33 individuals with metabolic syndrome in a longitudinal study before and after lifestyle-induced WL in a well-defined cohort. The 6-month WL intervention resulted in reduced BMI (-13.7%), improved insulin sensitivity (HOMA-IR, -46.1%), and reduced levels of circulating hsCRP (-39.9%), indicating metabolic syndrome reversal. The metaprotein spectra revealed a decrease of human proteins associated with gut inflammation. Taxonomic analysis revealed only minor changes in the bacterial composition with an increase of the families Desulfovibrionaceae, Leptospiraceae, Syntrophomonadaceae, Thermotogaceae and Verrucomicrobiaceae. Yet we detected an increased abundance of microbial metaprotein spectra that suggest an enhanced hydrolysis of complex carbohydrates. Hence, lifestyle-induced WL was associated with reduced gut inflammation and functional changes of human and microbial enzymes for carbohydrate hydrolysis while the taxonomic composition of the gut microbiome remained almost stable. The metaproteomics workflow has proven to be a suitable method for monitoring inflammatory changes in the fecal metaproteome.

Enzymatically synthesized α-galactooligosaccharides attenuate metabolic syndrome in high-fat diet induced mice in association with the modulation of gut microbiota.

The composition and structure of gut microbiota plays an important role in obesity induced by a high-fat diet (HFD) and related metabolic syndrome (MetS). Previous studies have shown that galacto-oligosaccharides (GOSs) have an effective anti-obesity effect. In this study, we aimed to investigate the effect of enzymatically synthesized α-galacto-oligosaccharides (ES-α-GOSs) on MetS and gut microbiota dysbiosis in HFD-fed mice, and to further investigate whether the attenuation of MetS is associated with the modulation of gut microbiota. Our results indicated that ES-α-GOS could notably ameliorate obesity-related MetS, including hyperlipidemia, insulin resistance and mild inflammation. The subsequent analysis of gut microbiota further showed that ES-α-GOS supplements can significantly modulate the overall composition of the gut microbiota and reverse the gut microbiota disorder caused by HFD feeding. Moreover, Spearman correlation analysis showed that 40 key bacteria reversed by ES-α-GOS were highly associated with metabolic parameters. These results suggested that ES-α-GOSs could serve as a potential candidate for preventing obesity-induced MetS in association with the modulation of gut microbiota.