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Recently, cyclomodulins have been identified in Escherichia coli (E. coli), which can induce dysplastic damage. This work aimed to determine the dysplastic activity of cyclomodulin-harboring E. coli isolated from CRC patients, obese and normal-weight subjects in a mouse model. Forty-two mice were pretreated with streptomycin, azoxymethane, and dextran sodium sulfate. Mice were infected with E. coli pks + isolated from a CRC patient, with E. coli pks + cif + isolated from obese or normal-weight subjects, or with E. coli HB101. The presence of cyclomodulin-harboring E. coli in the feces, weight loss, changes in fecal consistency, and the presence of blood in the feces were monitored and used to assess the disease activity index (DAI). After 62 days, the mice were sacrificed to evaluate the presence of intestinal polyps and dysplastic damage by histologic sections. Cyclomodulin-harboring E. coli colonized the mice; these mice exhibited weight loss and watery diarrhea, and isolated normal-weight E. coli had a higher DAI. Polyps were observed in mice infected with cyclomodulin-harboring E. coli in the ileum but to a greater extent in obese isolates. E. coli isolated from CRC showed more significant endothelial damage associated with dysplasia in the ileum in equal proportions from obese and normal-weight isolates. In conclusion, E. coli harboring cyclomodulins isolated from CRC, obesity, or normal weight can cause dysplastic damage in the ileum of mice and may be a risk factor for CRC development., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Objective: Metabolic and bariatric surgery (MBS) is associated with substantial, but variable, weight outcomes. The gut microbiome may be a factor in determining weight trajectory, but examination has been limited by a lack of longitudinal studies with robust microbiome sequencing. This study aimed to describe changes in the microbiome and associations with weight outcomes more than 2 years post surgery., Methods: Data were collected at two Midwestern U.S., Centers: Adults undergoing primary MBS were assessed before and 1, 6, 12, 18, and 24 months after surgery. BMI and metagenomic sequencing occurred at each assessment. A linear growth mixture model determined class structure for weight trajectory., Results: A linear growth mixture model of participants (N = 124) revealed a two-class structure; one class had greater sustained weight loss relative to the other. Greater genus-level taxonomic changes in the microbiome composition at each time point were associated with being in the more favorable weight trajectory class, after controlling for surgery type. Higher Proteobacteria relative abundance at 1 month was predictive of percentage weight change at 6, 12, 18, and 24 months (p < 0.05 for all)., Conclusions: Greater genus-level taxonomic changes in the gut microbiota are associated with improved weight trajectory. Early changes in the gut microbiota may be an important indicator of MBS outcomes and durability., (© 2024 The Obesity Society.)

Objective: Obesity continues to be a major problem, despite known treatment strategies such as lifestyle modifications, pharmaceuticals, and surgical options, necessitating the development of novel weight loss approaches. The naturally occurring fatty acid, 10,12 conjugated linoleic acid (10,12 CLA), promotes weight loss by increasing fat oxidation and browning of white adipose tissue, leading to increased energy expenditure in obese mice. Coincident with weight loss, 10,12 CLA also alters the murine gut microbiota by enriching for microbes that produce short chain fatty acids (SCFAs), with concurrent elevations in fecal butyrate and plasma acetate., Methods: To determine if the observed microbiota changes are required for 10,12 CLA-mediated weight loss, adult male mice with diet-induced obesity were given broad-spectrum antibiotics (ABX) to perturb the microbiota prior to and during 10,12 CLA-mediated weight loss. Conversely, to determine whether gut microbes were sufficient to induce weight loss, conventionally-raised and germ-free mice were transplanted with cecal contents from mice that had undergone weight loss by 10,12 CLA supplementation., Results: While body weight was minimally modulated by ABX-mediated perturbation of gut bacterial populations, adult male mice given ABX were more resistant to the increased energy expenditure and fat loss that are induced by 10,12 CLA supplementation. Transplanting cecal contents from donor mice losing weight due to oral 10,12 CLA consumption into conventional or germ-free mice led to improved glucose metabolism with increased butyrate production., Conclusions: These data suggest a critical role for the microbiota in diet-modulated changes in energy balance and glucose metabolism, and distinguish the metabolic effects of orally delivered 10,12 CLA from cecal transplantation of the resulting microbiota., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Systemic inflammation is reported in normal-weight obesity (NWO) and metabolically healthy obesity (MHO), which may be linked to their increased cardiovascular disease (CVD) risk. Yet, drivers of this inflammation remain unclear. We characterized factors known to influence inflammatory status (i.e., intestinal permeability, adipose tissue, diet quality, microbiota), and their relationships with measured inflammation, in NWO and MHO, healthy control subjects (CON), and metabolically unhealthy obesity (MUO; N = 80; n = 20/group). Serum indicators of intestinal permeability and inflammation were assessed by ELISA and/or multiplex. Total, visceral, and percent body fat were measured with dual-energy X-ray absorptiometry (DXA). Fecal microbiota composition was assessed via 16S rRNA sequencing ( n = 9-10/group). For C-reactive protein (CRP), MUO > NWO > CON ( P < 0.0001). In MHO, CRP was intermediate and similar to both MUO and NWO. Lipopolysaccharide binding protein (LBP) and the ratio of LBP to soluble CD14 (sCD14) were higher in MHO and MUO vs. CON/NWO ( P < 0.0001). Across correlation and regression analyses, LBP consistently displayed the strongest relationships with CRP in the entire sample ( r = 0.78; β = 0.57; P < 0.0001) and in MHO ( r = 0.74; P < 0.01) but not NWO ( r = 0.37; P = 0.11). Shannon index was higher in CON compared with MUO ( P < 0.05) and inversely correlated with CRP in the full sample ( r = -0.37; P < 0.05). These data are consistent with the notion that intestinal permeability is associated with low-grade inflammation in MHO, which could be implicated in this population's reported CVD risk. NEW & NOTEWORTHY This is the first study to our knowledge to examine biomarkers of intestinal permeability in normal-weight obesity and one of few assessing microbiota compositions in this population. Additionally, we report that individuals with metabolically healthy obesity and metabolically unhealthy obesity displayed similar evidence of intestinal permeability, which was more strongly associated with systemic inflammation than total and visceral adipose tissue mass.

Background: Obesity and diabetes mellitus (DM) have become public health concerns worldwide. Both conditions have severe consequences and are associated with significant medical costs and productivity loss. Additionally, Helicobacter pylori infection may be a risk factor for the development of these conditions. However, whether eradicating H. pylori infection directly causes weight loss or improves insulin sensitivity is unknown., Methods: In this study, we confirmed the effect of sleeve gastrectomy according to the state of the gastric microbiota in 40 patients with obesity, DM, and H. pylori infection. Patients with obesity were divided into four groups: non-DM without H. pylori infection (ND), non-DM with H. pylori infection (ND-HP), DM, and DM with H. pylori infection (DM-HP) using 16S V3-V4 sequencing., Results: In the DM group, ALT, hemoglobin, HbA1c, blood glucose, and HSI significantly decreased, whereas high-density lipoprotein significantly increased. However, in the H. pylori-positive group, no significant difference was observed. The diversity of gastric microbiota decreased in the order of the ND > DM > ND-HP > DM-HP groups. We also conducted a correlation analysis between the preoperative microbes and clinical data. In the ND-HP group, most of the top 20 gastric microbiota were negatively correlated with glucose metabolism. However, H. pylori infection was positively correlated with pre-insulin levels., Conclusion: Therefore, these findings indicate that patients with obesity and diabetes clearly benefit from surgery, but H. pylori infection may also affect clinical improvement., (© 2024. The Author(s).)

Various roles of intestinal flora in the gut-brain axis response pathway have received enormous attention because of their unique position in intestinal flora-derived metabolites regulating hormones, inducing appetite, and modulating energy metabolism. Reward pathways in the brain play a crucial role in gut-brain communications, but the mechanisms have not been methodically understood. This review outlined the mechanisms by which leptin, ghrelin, and insulin are influenced by intestinal flora-derived metabolites to regulate appetite and body weight, focused on the significance of the paraventricular nucleus and ventromedial prefrontal cortex in food reward. The vagus nerve and mitochondria are essential pathways of the intestinal flora involved in the modulation of neurotransmitters, neural signaling, and neurotransmission in gut-brain communications. The dynamic response to nutrient intake and changes in the characteristics of feeding activity requires the participation of the vagus nerve to transmit messages to be completed. SCFAs, Bas, BCAAs, and induced hormones mediate the sensory information and reward signaling of the host in the complex regulatory mechanism of food selection, and the composition of the intestinal flora significantly impacts this process. Food reward in the process of obesity based on gut-brain communications expands new ideas for the prevention and treatment of obesity.

Enigmatic sarcopenic obesity is still a challenge for science and adds to the global public health burden. The progressive accumulation of body fat combined with a dysfunctional skeletal muscle structure and composition, oxidative stress, mitochondrial dysfunction, and anabolic resistance, among other aggravating factors, together represent the seriousness and complexity of treating the metabolic disorder of sarcobesity in aging. For this reason, further studies are needed that encourage the support of therapeutic management. It is along these lines that we direct the reader to therapeutic approaches that demonstrate important, but still obscure, outcomes in the physiological conditions of sarcobesity, such as the role of taurine in modulating inflammatory and antioxidant mechanisms in muscle and adipose tissue, as well as the management of gut microbiota, able to systemically re-establish the structure and function of the gut-muscle axis, in addition to the merits of physical exercise as an instrument to improve muscular health and lifestyle quality., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The gut microbiome, body weight, and related comorbidities are intricately linked through a complex interaction of microbial, genetic, environmental, and psychological factors. Alterations in gut microbiota can contribute to the development of weight disorders and depressive symptoms, with the potential for these relationships to be bidirectional. Effective management of these interconnected conditions often involves a combination of lifestyle modifications and psychological support. Medical interventions, including treatments for obesity, antidiabetic drugs, antidepressants, antibiotics, and probiotics, can have beneficial and detrimental effects on gut microbiota and mental health. Further research is needed to better understand their impact on gut microbiome and mental health in the context of obesity., (© 2024. The Author(s).)

Background: Obesity in humans can lead to chronic diseases such as diabetes and cardiovascular disease. Similarly, subcutaneous fat (SCF) in pigs affects feed utilization, and excessive SCF can reduce the feed efficiency of pigs. Therefore, identifying factors that suppress fat deposition is particularly important. Numerous studies have implicated the gut microbiome in pigs' fat deposition, but research into its suppression remains scarce. The Lulai black pig (LL) is a hybrid breed derived from the Laiwu pig (LW) and the Yorkshire pig, with lower levels of SCF compared to the LW. In this study, we focused on these breeds to identify microbiota that regulate fat deposition. The key questions were: Which microbial populations reduce fat in LL pigs compared to LW pigs, and what is the underlying regulatory mechanism?, Results: In this study, we identified four different microbial strains, Eubacterium siraeum, Treponema bryantii, Clostridium sp. CAG:413, and Jeotgalibaca dankookensis, prevalent in both LW and LL pigs. Blood metabolome analysis revealed 49 differential metabolites, including tanshinone IIA and royal jelly acid, known for their anti-adipogenic properties. E. siraeum was strongly correlated with these metabolites, and its genes and metabolites were enriched in pathways linked to fatty acid degradation, glycerophospholipid, and glycerolipid metabolism. In vivo mouse experiments confirmed that E. siraeum metabolites curb weight gain, reduce SCF adipocyte size, increase the number of brown adipocytes, and regulate leptin, IL-6, and insulin secretion. Finally, we found that one important pathway through which E. siraeum inhibits fat deposition is by suppressing the phosphorylation of key proteins in the PI3K/AKT signaling pathway through the reduction of tyrosine., Conclusions: We compared LW and LL pigs using fecal metagenomics, metabolomics, and blood metabolomics, identifying E. siraeum as a strain linked to fat deposition. Oral administration experiments in mice demonstrated that E. siraeum effectively inhibits fat accumulation, primarily through the suppression of the PI3K/AKT signaling pathway, a critical regulator of lipid metabolism. These findings provide a valuable theoretical basis for improving pork quality and offer insights relevant to the study of human obesity and related chronic metabolic diseases. Video Abstract., (© 2024. The Author(s).)

Green tea polyphenols (GTP) have been shown to ameliorate lipid metabolic disorders by regulating intestinal bacteria. Given the significant role of intestinal bacteriophages in shaping the gut microbiota, this study investigates GTP's influence on gut bacteriophage-bacteria interactions and lipid metabolism using metagenomics and metabonomics. The research results indicated that GTP significantly reduced body weight, serum triglycerides, leptin, insulin resistance, interleukin-6, and TNF-α levels while increasing adiponectin in ob/ob mice fed high-fat diet, aiding intestinal repair. GTP improved gut health by decreasing Enterobacter, Siphoviridae and Enterobacteria&#95;phage&#95;sfv, increasing Bifidobacterium and intestinal metabolites SCFA and hippuric acid. Correlation analysis showed negative correlations between Enterobacter sp. 50,588,862 and Enterobacteria&#95;phages, Shigella&#95;phages with 4-hydroxyphenylpyruvate and hippuric acid. Bifidobacterium choerinum and Bifidobacterium sp. AGR2158 were positively correlated with fatty acids and bile acids. In conclusion, GTP reduced fat accumulation and inflammation, enhanced gut barrier function in obese mice, closely associated with changes in the gut bacteriophage community., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

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, PPARβ, PPARγ, C/EBPα, C/EBPβ, 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 × 10 8  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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. The authors declare no conflict of interest., (Copyright © 2024. Published by Elsevier Inc.)

Obesity has become a serious epidemic problem in the world, and probiotics and prebiotics have been used to treat obesity. The effectiveness of diet therapy such as Clostridium butyricum (CB) and inulin supplementation in obesity and whether they can cooperate to produce better effects are still unclear. And during this process, intestinal flora play an important role, while the bacteria involved and the metabolic mechanism need to be explored. In this study, we successfully established a mouse obesity model with a high-fat diet (HFD) and divided it into three experimental groups: 7% CB (CB7), 7% CB + 1% inulin (C7G1), and 10% CB + 1% inulin (C10G). Dietary supplementation with CB and inulin could improve the glucose tolerance and intestinal microbial composition of obese mice, among which the simultaneous supplementation with 7% CB and 1% inulin (C7G1) has the most significant effect on obese mice fed with a HFD. It could significantly reduce the amount of total cholesterol, triglyceride, and low-density lipoprotein, improve abnormal glucose tolerance, and reduce abnormal blood glucose in obese mice. The intestinal flora of obese mice changed significantly, among which Lachnospiraceae&#95;unclassified , Porphyromonaceae&#95;unclassified , Olsenella , Bacteria&#95;unclassified and Clostridiales&#95;unclassified decreased due to the HFD, while Megamonas and Clostridium XIVa increased. After the supplementation with CB and inulin, the enrichment of three kinds of beneficial bacteria, Parabacteroides, Bacteroides , and Ruminococcaceae unclassified increased. The high-fat diet could upregulate the expression of FGF21, and the Clostridium butyricum and inulin supplemented diet could decrease the upregulation.

This study investigates the effects of bariatric surgery on non-alcoholic fatty liver disease (NAFLD) by examining the interplay between gut microbiota, epigenetics, and metabolic health. A cohort of 22 patients undergoing sleeve gastrectomy (SG) was analyzed for changes in gut microbial composition and DNA methylation profiles before and six months after surgery. Correlations between gut microbial abundance and clinical markers at baseline revealed that certain genera were associated with worse metabolic health and liver markers. Following SG, significant improvements were observed in the clinical, anthropometric, and biochemical parameters of the NAFLD patients. Although alpha-diversity indices (i.e., Chao1, Simpson, Shannon) did not show significant changes, beta-diversity analysis revealed a slight shift in microbial composition (PERMANOVA, p = 0.036). Differential abundance analysis identified significant changes in specific bacterial taxa, including an increase in beneficial Lactobacillus species such as Lactobacillus crispatus and Lactobacillus iners and a decrease in harmful taxa like Erysipelotrichia. Additionally, DNA methylation analysis revealed 609 significant differentially methylated CpG sites between the baseline values and six months post-surgery, with notable enrichment in genes related to the autophagy pathway, such as IRS4 and ATG4B . The results highlight the individualized responses to bariatric surgery and underscore the potential for personalized treatment strategies. In conclusion, integrating gut microbiota and epigenetic factors into NAFLD management could enhance treatment outcomes, suggesting that future research should explore microbiome-targeted therapies and long-term follow-ups on liver health post-surgery.

The prevalence of obesity in dogs is increasing worldwide. This study evaluated the effects of a mixed probiotic formula on the weight, body condition score (BCS), blood metabolite profiles, and gut microbiota of overweight and obese dogs over a 12-week supplementation period to determine the anti-obesity effects of Lactiplantibacillus plantarum CBT LP3 and Bifidobacterium breve CBT BR3. This was a community-based, randomized study that sampled 41 overweight and obese dogs with a veterinarian-determined BCS of 6 or more. The physical activity of all the subjects was measured using a pedometer designed exclusively for dogs. The food intake was measured using the developed application. Only the treatment group received the mixed probiotic formula twice daily (3 g per dose). A significant decrease in body weight (p < 0.0001), BCS (p < 0.0001), serum TG (p < 0.0001), serum TC (p = 0.0400), and serum leptin (p = 0.0252), and a significantly increased serum adiponectin levels (p = 0.0007) were observed in the treatment group compared with the values in the control group. Microbiota analysis showed that Lactiplantibacillus increased and Erysipelatoclostridium, Staphylococcus, and Gemella decreased more significantly in the treatment group than in the control group. These results suggested that Lactiplantibacillus plantarum CBT LP3 and Bifidobacterium breve CBT BR3 may be effective in alleviating obesity in dogs., (© 2024. The Author(s).)

Overweight and obesity are major and increasingly global public health concern. High intake of dietary fiber is negatively correlated with obesity and obesity-related metabolic diseases. Here, we investigated the impact of arabinoxylan on obesity based on the modification of gut microecology. Arabionxylan reduced body weight and improved glucose metabolism, as well as intestinal barrier function and metabolic endotoxemia in obese mice. Supplementation with arabinoxylan increased the relative abundance of Prevotellaceae&#95;UCG&#95;001 , Lachnospiraceae&#95;NK4A136&#95;group , Clostridia&#95;UCG&#95;014 , Alistipes , Bacteroides , and Ruminococcus, which was associated with the upregulated 7α-dehydroxylation function and production of secondary bile acids (deoxycholic acid and lithocholic acid). The modification of gut microbiota by arabinoxylan also influenced the production of SCFAs, genistein, daidzein, indolelactic acid, and indoleacetic acid, contributing to the amelioration of obesity. Our study highlights the antiobesity effects of arabinoxylan through the modification of gut microbiota and the production of bioactive metabolites.

The gut microbiota influences physiological functions of the host, ranging from the maintenance of local gut homeostasis to systemic immunity and metabolism. Secreted phospholipase A 2 group X (sPLA 2 -X) is abundantly expressed in colonic epithelial cells but is barely detectable in metabolic and immune tissues. Despite this distribution, sPLA 2 -X-deficient (Pla2g10 -/- ) mice displayed variable obesity-related phenotypes that were abrogated after treatment with antibiotics or cohousing with Pla2g10 +/+ mice, suggesting the involvement of the gut microbiota. Under housing conditions where Pla2g10 -/- mice showed aggravation of diet-induced obesity and insulin resistance, they displayed increased colonic inflammation and epithelial damage, reduced production of polyunsaturated fatty acids (PUFAs) and lysophospholipids, decreased abundance of several Clostridium species, and reduced levels of short-chain fatty acids (SCFAs). These obesity-related phenotypes in Pla2g10 -/- mice were reversed by dietary supplementation with ω3 PUFAs or SCFAs. Thus, colonic sPLA 2 -X orchestrates ω3 PUFA-SCFA interplay via modulation of the gut microbiota, thereby secondarily affecting systemic metabolism., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Obesity is a costly and ongoing health complication in the United States and globally. Bioactive-rich foods, especially those providing polyphenols, represent an emerging and attractive strategy to address this issue. Berry-derived anthocyanins and their metabolites are of particular interest for their bioactive effects, including weight maintenance and protection from metabolic aberrations. Earlier findings from small clinical trials suggest modulation of substrate oxidation and glucose tolerance with mediation of prospective benefits attributable to the gut microbiota, but mixed results suggest appropriate anthocyanin dosing poses a challenge. The objective of this randomized, placebo-controlled study was to determine if anthocyanin-dense elderberry juice (EBJ) reproduces glucoregulatory and substrate oxidation effects observed with other berries and if this is mediated by the gut microbiota. Overweight or obese adults (BMI > 25 kg/m 2 ) without chronic illnesses were randomized to a 5-week crossover study protocol with two 1-week periods of twice-daily EBJ or placebo (PL) separated by a washout period. Each treatment period included 4 days of controlled feeding with a 40% fat diet to allow for comparison of measurements in fecal microbiota, meal tolerance testing (MTT), and indirect calorimetry between test beverages. Eighteen study volunteers completed the study. At the phylum level, EBJ significantly increased Firmicutes and Actinobacteria, and decreased Bacteroidetes. At the genus level, EBJ increased Faecalibacterium , Ruminococcaceae , and Bifidobacterium and decreased Bacteroides and lactic acid-producing bacteria, indicating a positive response to EBJ. Supporting the changes to the microbiota, the EBJ treatment significantly reduced blood glucose following the MTT. Fat oxidation also increased significantly both during the MTT and 30 min of moderate physical activity with the EBJ treatment. Our findings confirm the bioactivity of EBJ-sourced anthocyanins on outcomes related to gut health and obesity. Follow-up investigation is needed to confirm our findings and to test for longer durations.

Background/objectives: Obesity impairs intestinal glucose uptake (GU) (intestinal uptake of circulating glucose from blood) and alters gut microbiome. Exercise improves intestinal insulin-stimulated GU and alters microbiome. Genetics influence the risk of obesity and gut microbiome. However, the role of genetics on the effects of exercise on intestinal GU and microbiome is unclear., Methods: Twelve monozygotic twin pairs discordant for BMI (age 40.4 ± 4.5 years, BMI heavier 36.7 ± 6.0, leaner 29.1 ± 5.7, 8 female pairs) performed a six-month-long training intervention. Small intestine and colonic insulin-stimulated GU was studied using [ 18 F]FDG-PET and microbiota from fecal samples with 16s rRNA., Results: Ten pairs completed the intervention. At baseline, heavier twins had lower small intestine and colonic GU ( p < 0.05). Response to exercise differed between twins ( p = 0.05), with leaner twins increasing colonic GU. Alpha and beta diversity did not differ at baseline. During the intervention, beta diversity changed significantly, most prominently at the mid-point ( p < 0.01). Beta diversity changes were only significant in the leaner twins when the twin groups were analyzed separately. Exercise was associated with changes at the phylum level, mainly at the mid-point (pFDR < 0.05); at the genus level, several microbes increased, such as Lactobacillus and Sellimonas (pFDR < 0.05). In type 1 analyses, many genera changes were associated with exercise, and fewer, such as Lactobacillus , were also associated with dietary sugar consumption ( p < 0.05)., Conclusions: Obesity impairs insulin-stimulated intestinal GU independent of genetics. Though both twin groups exhibited some microbiota changes, most changes in insulin-stimulated colon GU and microbiota were significant in the leaner twins.

Obesity is a serious global health issue. Emerging evidence indicates that the gut microbiota may contribute to the development of obesity, possibly by instigating inflammatory processes. The objective of this research is to conduct a comparative analysis of the gut microbiota composition in obese and normal-weight Uygur adults, while examining the associations with adipocyte-related factors and dietary variables. According to the inclusion and exclusion criteria, twenty-seven Uygur adults with obesity and twenty Uygur adults with normal-weight were recruited from a local community. Anthropometric measurements and blood samples were collected. Gut microbiota composition was analyzed using 16 S rRNA gene sequencing. Adipocyte-related factors were measured using enzyme-linked immunosorbent assay (ELISA). Statistical analyses were performed to compare the gut microbiota composition between the two groups and to identify correlations between gut microbiota and adipocyte-related factors. Compared with the normal-weight group, the obese group exhibited a marked reduction in both diversity and richness of the gut microbiota, alongside a decrease in Ruminococcaceae&#95;UCG&#95;014, Coprococcus&#95;2, and Parabacteroides, and an increase in Megamonas and Lachnoclostridium, implying a potential link to the development of obesity. Individuals with obesity were found to have higher Leptin (LEP), Interleukin-6 (IL-6), and C-reactive protein (CRP) than normal-weight individuals. Obese Uygur adults exhibited a gut microbiota characterized by diminished diversity and richness relative to normal-weight individuals. Parabacteroides, Megamonas, and Lachnoclostridium may play an important role in the development of obesity in Uygur population. Underlying mechanisms need further investigation., (© 2024. The Author(s).)

Background: Although numerous studies have shown that bariatric surgery results in sustained weight loss and modifications in gut microbiota composition and cognitive function, the exact underlying mechanisms are unclear. This study aimed to investigate the effects of bariatric surgery on cognitive function through the microbiota-gut-brain axis (MGBA)., Methods: Demographic data, serum samples, fecal samples, cognitive assessment scales, and resting-state functional connectivity magnetic resonance imaging (rs-fMRI) scans were obtained from 39 obese patients before and after (6 months) laparoscopic sleeve gastrectomy (LSG). PCA analysis, OPLS-DA analysis, and permutation tests were used to conduct fecal 16 S microbiota profiling, serum metabolomics, and neuroimaging analyses, and a bariatric surgery-specific rs-fMRI brain functional connectivity network was constructed. Spearman correlation analysis and Co-inertia analysis were employed to correlate significant alterations in cognitive assessment scales and resting-state functional connectivity difference networks with differential serum metabolites and 16 S microbiota data to identify key gut microbiota and serum metabolic factors., Results: LSG significantly reduced the weight of obese patients, with reductions of up to 28%. Furthermore, cognitive assessment scale measurements revealed that LSG enhanced cognitive functions, including memory (HVLT, p = 0.000) and executive function (SCWT, p = 0.008). Also, LSG significantly altered gut microbiota composition (p = 0.001), with increased microbial abundance and diversity (p < 0.05). Moreover, serum metabolite levels were significantly altered, revealing intergroup differences in 229 metabolites mapped to 72 metabolic pathways (p < 0.05, VIP > 1). Spearman correlation analysis among cognitive assessment scales, gut microbiota species, and serum metabolites revealed correlations with 68 gut microbiota species and 138 serum metabolites (p < 0.05). Furthermore, pairwise correlations were detected between gut microbiota and serum metabolites (p < 0.05). Functional neuroimaging analysis revealed that LSG increased functional connectivity in cognitive-related frontotemporal networks (FPN, p < 0.01). Additionally, normalization of the default mode network (DMN) and salience network (SN) connectivity was observed after LSG (p < 0.001). Further canonical correlation and correlation analysis suggested that the cognitive-related brain network changes induced by LSG were associated with key gut microbiota species (Akkermansia, Blautia, Collinsella, Phascolarctobacterium, and Ruminococcus, p < 0.05) and neuroactive metabolites (Glycine, L-Serine, DL-Dopa, SM (d18:1/24:1(15Z), p < 0.05)., Conclusion: These findings indicate the pathophysiological role of the microbiota-gut-brain axis in enhancing cognitive function after bariatric surgery, and the study provides a basis for clinical dietary adjustments, probiotic supplementation, and guidance for bariatric surgery, but further research is still needed., Trial Registration: Chinese Clinical Trial Registry, ChiCTR2100049403. Registered 02 August 2021, https://www.chictr.org.cn/ ., (© 2024. The Author(s).)

The gut microbiota (GM), comprising trillions of microorganisms in the gastrointestinal tract, is a key player in the development of obesity and related metabolic disorders, such as type 2 diabetes (T2D), metabolic syndrome (MS), and cardiovascular diseases. This mini-review delves into the intricate roles and mechanisms of the GM in these conditions, offering insights into potential therapeutic strategies targeting the microbiota. The review elucidates the diversity and development of the human GM, highlighting its pivotal functions in host physiology, including nutrient absorption, immune regulation, and energy metabolism. Studies show that GM dysbiosis is linked to increased energy extraction, altered metabolic pathways, and inflammation, contributing to obesity, MS, and T2D. The interplay between dietary habits and GM composition is explored, underscoring the influence of diet on microbial diversity and metabolic functions. Additionally, the review addresses the impact of common medications and therapeutic interventions like fecal microbiota transplantation on GM composition. The evidence so far advocates for further research to delineate the therapeutic potential of GM modulation in mitigating obesity and metabolic diseases, emphasizing the necessity of clinical trials to establish effective and sustainable treatment protocols., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.)

The potential effects of probiotics on lowering lipid accumulation and alleviating gut microbiota perturbation have been extensively substantiated, but whether Lactobacillus rhamnoses -fermented oyster mushroom (FOM) could more pronouncedly attenuate obesity remains unclear. In this study, the anti-obesity effect of FOM was estimated based on the gut microbiota profile and analysis of hepatic lipid metabolic characteristics. The results revealed that FOM intervention dramatically improved hepatic lipid accumulation, characterized by reduction in fat-related factor metabolism levels and liver lesion enzymatic activities and down-regulation of the expression of genes associated with glycolipid metabolism ( Foxo1 , Gck , G6pd , Il6r and IL-β ). Metabolomics analysis indicated HFD-induced dysglycaemia and disturbed amino acid metabolism, characterized by significant enrichment of pathways (butanoate metabolism, arginine biosynthesis, etc .) and elevated levels of D-mannose, succinate and β-D-fructose, followed by a decreased galactitol content. Furthermore, FOM intervention showed significant enrichment of specific pathways, particularly transcriptional misregulation in cancer and FoxO signaling pathways, while the MAPK signaling pathway demonstrated consistent enrichment across all experimental groups. FOM intervention reshaped the gut microbiota structure by facilitating the proliferation of SCFA producers ( Romboutsia , Ruminococcaceae and Allobaculum ), together with the depletion of Lachnospiraceae population. The current study strengthened our understanding of FOM prebiotic activities and obesity alleviation mechanisms.

Background: Obesity is a growing health concern in China, closely linked to metabolic disorders such as type 2 diabetes. Laparoscopic Sleeve Gastrectomy (LSG) is effective in promoting weight loss and improving metabolic outcomes. Emerging evidence highlights the role of gut microbiota in metabolic regulation, yet the specific alterations in gut microbiota and their association with metabolic changes post-surgery in Chinese patients remain unclear. Understanding these shifts could provide key insights into optimizing treatment strategies for metabolic improvement following bariatric surgery., Methods: Stool samples and clinical data were collected from 30 obese patients before and 6 months after surgery. The composition of the gut microbiota was analyzed through 16S rRNA sequencing, and Spearman correlation analysis was used to determine the association between gut microbiota and clinical indicators., Results: The analysis of 30 patients showed a significant decrease in Body Mass Index (BMI) (36.75 ± 4.09 kg/m 2 vs 26.37 ± 3.47 kg/m 2 , p < 0.0001). Glucose metabolism, including Hemoglobin A1C levels, improved significantly (6.05 ± 0.96 vs 5.05 ± 0.25, p < 0.0001), and liver function as well as serum lipid levels were also notably improved. LSG increased the richness and composition of gut microbiota in obese patients post-surgery. These changes in gut microbiota were closely associated with improved clinical metabolic parameters., Conclusion: LSG not only significantly reduces body weight while also alleviating metabolic syndrome and comorbidities by altering gut microbiota., (© 2024. The Author(s).)

Probiotics, known for regulating gut microbiota, may aid those with overweight or obesity, but their mechanisms require more research. This study involved 75 overweight or obese young adults, randomly assigned to either a Bifidobacterium breve BBr60 (BBr60) group or a placebo group. Both groups received diet guidance and took either BBr60 (1 × 10 10 CFU/day) or a placebo for 12 weeks. Researchers analyzed body composition, serum glucose, lipids, liver and kidney function, comprehensive metabolome, and intestinal homeostasis before and after the intervention. After 12 weeks, BBr60 significantly reduced weight and BMI compared to pretreatment levels and outperformed the placebo. The BBr60 group also showed improved blood biochemistry, with notably lower fasting blood glucose (FBG) levels than the placebo group ( p < 0.05). Additionally, BBr60 influenced vital serum and fecal metabolites related to three amino acid metabolic pathways and regulated the bacteria Dialister , Klebsiella , and Bacteroides , which correlated strongly with serum metabolites. These findings indicate that BBr60 can safely and effectively regulate BMI, body weight, serum glucose, lipids, and liver function markers, which may involve BBr60's impact on key gut bacteria, which influence metabolites related to the valine, leucine, and isoleucine biosynthesis; glycine, serine, and threonine metabolism; and alanine, aspartate, and glutamate metabolism.

The gut microbiome may be related to the prevalence of overweight and obesity, but high interindividual variability of the human microbiome complicates our understanding. Obesity often occurs concomitantly with micronutrient deficiencies that impair energy metabolism. Microbiota composition is affected by diet. Host-microbiota interactions are bidirectional. We propose three pathways whereby these interactions may modulate the gut microbiome and obesity: (1) ingested compounds or derivatives affecting small intestinal transit, endogenous secretions, digestion, absorption, microbiome balance, and gut barrier function directly affect host metabolism; (2) substrate availability affecting colonic microbial composition and contact with the gut barrier; and (3) microbial end products affecting host metabolism. The quantity/concentration, duration, and/or frequency (circadian rhythm) of changes in these pathways can alter the gut microbiome, disrupt the gut barrier, alter host immunity, and increase the risk of and progression to overweight and obesity. Host-specific characteristics (e.g., genetic variations) may further affect individual sensitivity and/or resilience to diet- and microbiome-associated perturbations in the colonic environment. In this narrative review, the effects of selected interventions, including fecal microbiota transplantation, dietary calorie restriction, dietary fibers and prebiotics, probiotics and synbiotics, vitamins, minerals, and fatty acids, on the gut microbiome, body weight, and/or adiposity are summarized to help identify mechanisms of action and research opportunities., (© 2024 The Author(s). Annals of the New York Academy of Sciences published by Wiley Periodicals LLC on behalf of The New York Academy of Sciences.)

Background: Pre-pregnancy overweight and obesity promote deleterious health impacts on both mothers during pregnancy and the offspring. Significant changes in the maternal peripheral blood mononuclear cells (PBMCs) gene expression due to obesity are well-known. However, the impact of pre-pregnancy overweight on immune cell gene expression during pregnancy and its association with maternal and infant outcomes is not well explored., Methods: Blood samples were collected from healthy normal weight (NW, pre-pregnancy BMI 18.5-24.9) or overweight (OW, pre-pregnancy BMI 25-29.9) 2nd parity pregnant women at 12, 24 and 36 weeks of pregnancy. PBMCs were isolated from the blood and subjected to mRNA sequencing. Maternal and infant microbiota were analyzed by 16S rRNA gene sequencing. Integrative multi-omics data analysis was performed to evaluate the association of gene expression with maternal diet, gut microbiota, milk composition, and infant gut microbiota., Results: Gene expression analysis revealed that 453 genes were differentially expressed in the OW women compared to NW women at 12 weeks of pregnancy, out of which 354 were upregulated and 99 were downregulated. Several up-regulated genes in the OW group were enriched in inflammatory, chemokine-mediated signaling and regulation of interleukin-8 production-related pathways. At 36 weeks of pregnancy healthy eating index score was positively associated with several genes that include, DTD1, ELOC, GALNT8, ITGA6-AS1, KRT17P2, NPW, POT1-AS1 and RPL26. In addition, at 36 weeks of pregnancy, genes involved in adipocyte functions, such as NG2 and SMTNL1, were negatively correlated to human milk 2'FL and total fucosylated oligosaccharides content collected at 1 month postnatally. Furthermore, infant Akkermansia was positively associated with maternal PBMC anti-inflammatory genes that include CPS1 and RAB7B, at 12 and 36 weeks of pregnancy., Conclusions: These findings suggest that prepregnancy overweight impacts the immune cell gene expression profile, particularly at 12 weeks of pregnancy. Furthermore, deciphering the complex association of PBMC's gene expression levels with maternal gut microbiome and milk composition and infant gut microbiome may aid in developing strategies to mitigate obesity-mediated effects., Competing Interests: Declaration of competing interest No conflict of interests for all the authors., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Total saponins from Panax japonicus (TSPJ) have many beneficial physiological activities, particularly in alleviating the damages of aging and abnormal lipid metabolism. This work used mice models to investigate if TSPJ reduced obesity and regulated metabolic functions via the intestinal microbiota, the disturbance of which has been shown to cause aging-related diseases. The results showed that TSPJ significantly reduced the weight and blood lipid level of aging mice. Further analyses showed that TSPJ significantly inhibited adipogenesis, changed the composition of the intestinal flora, and protected the integrity of the intestinal barrier. It was inferred from the accumulated experimental data that TSPJ helped to combat obesity in aging mice by regulating the intestinal microbiota and promoting microbial metabolism., Competing Interests: Declaration of competing interest The authors declare no conflict of interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Obesity (OB) is a prevalent metabolic disorder. With the advancement of the economy, the prevention and treatment of obesity is a big problem for the global community. The methods to lose weight include exercise, diet, medicine, and surgery. Compared with other methods, diet regulation is safer and more effective. Hawthorn fruit has the effect of reducing weight, but the mechanism of effectiveness are not clear. In this study, obesity model rats are used to conduct scientific pharmacological research on hawthorn flavonoids. Hawthorn flavonoids can effectively improve the body weight, lipid accumulation, and lipid levels of obese rats. The contents of the colon of rats are analyzed using 16S rDNA sequencing technology. The intestinal microflora in obese rats changed significantly after flavonoids treatment, and they tended to be the control group. Based on liquid chromatography-mass spectrometry, serum metabolomics showed that the metabolites in the serum changed significantly, after hawthorn flavonoids treatment. Hawthorn flavonoids are especially involved in the biological processes of grade bile acid biosynthesis, histidine metabolism, and lipid metabolism. Pearson correlation analysis showed that the disorder of intestinal microorganisms is connected to changes in serum metabolites. These findings give a new idea about how hawthorn flavonoids help with obesity., (© 2024 Wiley‐VCH GmbH.)

Objective: Weight gain is a common side effect of antidepressive treatment, causing distress among patients and caretakers as it can lead to treatment discontinuation and complications such as diabetes type II and cardiovascular disease. Vortioxetine is one of the newer antidepressants and the pharmacodynamics differ from the selective serotonin reuptake inhibitors. It is marketed as being weight neutral; however, there is little evidence as to why. In recent years, there has been an increased focus on the faecal microbiota and its impact on body weight and mental and physical health. In the current work, we examine the effect of vortioxetine on weight gain and faecal microbiota composition., Methods: Forty male C57BL/6NTac mice were primed for 8 weeks with a high-fat diet (Hfd) or control diet (Cd), followed by a 4-week period on the same diet and additional +/- vortioxetine 10 mg/kg/daily., Results: Vortioxetine reduced Hfd-induced weight gain (Hfd + V: 8.2%, Hfd - V: 12.7%; p = 0.0374) but did not affect weight gain of the control group (Cd + V: 7.54%, Cd - V: 7.56%; p = 0.4944). Significant differences in faecal microbiota were observed in mice who received vortioxetine., Conclusion: Vortioxetine caused significant changes to the faecal microbiota composition and appeared to limit Hfd-induced weight gain., (© 2024 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society). Published by John Wiley & Sons Ltd.)

Background & Aims: Excess sucrose intake induces metabolic syndrome. In human, abnormal lipids metabolism like obesity, hyperlipidemia and fatty liver are induced. However, excess sucrose causes different phenotypes in different species. Based on our previous study, excess sucrose induced fatty liver and hyperlipidemia in rats. The phenotypes and mechanism of abnormal lipid metabolism in mice is unclear. We investigated the different phenotypes in 5 strains of mice and the relationship between gut microbiome and abnormal lipid metabolism in C57BL/6N mice., Methods: We examined the effect of a high sucrose diet in 5 different strains of mice. Besides, to find out the relationship between gut microbiome and metabolic disorder induced by excess sucrose, C57BL/6N mice were fed with a high sucrose diet with or without antibiotics cocktail., Results: A high sucrose diet induced obesity and fatty liver in inbred mice, whereas did not induce hyperlipidemia in all strains of mice. Moreover, a high sucrose diet changed the composition of gut microbiota in C57BL/6N mice. Antibiotics treatment alleviated the abnormal lipid metabolism induced by high sucrose diet by changing the composition of gut short chain fatty acids., Conclusions: These results indicates that the phenotypes of metabolic syndrome are influenced by genetic factors. Furthermore, the dysbiosis of gut microbiome caused by excess sucrose may contribute to the development of abnormal lipid metabolism via its metabolites., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)

Tea polyphenols have a regulatory effect on metabolic-related diseases, however, the underlying mechanism remains elusive. Our study aims to explore the dietary intervention effect of Epigallocatechin gallate (EGCG), the major polyphenol in green tea, on obesity and intestinal barrier disorders in mice fed a high-fat diet. By supplementing with 50 mg kg -1 EGCG, we observed a significant amelioration in body weight gain, fat accumulation, and liver dysfunction. Furthermore, EGCG modulated the HFD-induced metabolomic alterations. In particular, EGCG intervention restored the ileal barrier by enhancing the expression of tight junction proteins and antimicrobial peptides. At the mechanistic level, EGCG treatment stabilized hypoxia-inducible factor 1α (HIF1α) both in vitro and in vivo . Meanwhile, EGCG significantly increased the abundance of Dubosiella and Akkermansia , along with the elevated SCFA contents. These findings suggest that the ability of EGCG to stabilize HIF1α and regulate specific gut microbes is pivotal in mitigating ileal barrier dysfunction and obesity. Moreover, serum metabolomics revealed potential biomarkers following EGCG intervention. This study supports the intake of EGCG or green tea in obesity management and offers a novel perspective for investigating the metabolic regulatory mechanism of other dietary polyphenols.

Background and Aims: Intermittent fasting is a nutritional strategy that focuses on when to eat, rather than what to eat. Although the effectiveness of intermittent fasting practices in many metabolic diseases is known, its effect on microbiota and its underlying mechanism has not yet been clarified. This study aimed to investigate the effect of Ramadan fasting, one of the intermittent fasting practices, on gut microbiota and fatty acid binding protein 4 (FABP4)., Methods: The study involved 10 male volunteers, 6 of whom were overweight and 4 were obese. They fasted for an average of 14-15 hours daily from dawn to sunset during the 29-day Ramadan month between 23 March - 20 April 2023 and met the inclusion criteria. The participants' nutritional and physical activity status before and during Ramadan, as well as their anthropometric measurements before and after Ramadan, intestinal microbiota, transaminases, gamma-glutamyl transferase, C reactive protein, total cholesterol (C), high-density lipoprotein (HDL) C, low-density lipoprotein C, triglycerides (TG), and FABP4 levels, were evaluated within the scope of the study., Results: The study found a statistically significant increase in both alpha and beta diversity in the intestinal microbiota following Ramadan fasting (p<0.05). The F/B ratio, Firmicutes phylum, Clostridia class, Clostridiales order, and Ruminococcaceae family exhibited statistically significant decreases, while the Bacteroidetes and Proteobacteria phyla, Bacteroidia, Alphaproteobacteria, and Erysipelotrichi classes, Bacteroidales, Erysipelotrichales, and Actinomycetales orders, Erysipelotrichaceae family and Prevotella genus, demonstrated statistically significant increases (p<0.05). Participants who achieved an average weight loss of 2.3±0.99 kg at the end of Ramadan showed a significant increase in HDL-C and a significant decrease in TG levels (p<0.05). Although FABP4 levels decreased after fasting, this difference was not statistically significant (p>0.05)., Conclusion: Ramadan fasting induces weight loss, modifies gut microbiota, and improves blood lipid profile and FABP4 levels, suggesting the need for more extensive studies.

Seasonal rhythms are gaining attention given their impact on metabolic disorders development such as obesity gut microbiota is emerging as a key factor in mediating this link. However, the underlying mechanisms are still poorly understood. In this regard, corticosterone may play a role as it has been shown to be affected by gut bacteria and seasonal rhythms, and has been linked to obesity. Thus, this study aimed to investigate if seasonal rhythms effects on corticosterone are influenced by gut microbiota in obese rats and whether this may be related to seasonal and clock genes expression in the pituitary gland and colon. Fischer 344 male rats fed with cafeteria diet (CAF) were housed under different photoperiods for 9 weeks and treated with an antibiotic cocktail (ABX) in drinking water during the last 4 weeks. Rats fed with standard chow and CAF-fed rats without ABX were included as controls. ABX altered gut microbiota, corticosterone levels and seasonal clock expression in the pituitary depending on photoperiod conditions. These results suggest a link between gut bacteria, seasonal rhythms and corticosterone and a novel nutrigenomic target for obesity., (© 2024. The Author(s).)

The ketogenic diet (KD) is a popular option for managing body weight, though its influence on glucose and lipid metabolism was still inconclusive. Gut microbiota is modulated by dietary pattens and has been associated with the changes of metabolic homeostasis induced by KD. Here, we found that two types of KDs, KD1 (8.8% carbohydrate, 73.4% fat, 17.9% protein, 5.7 kcal/g) and KD2 (0.4% carbohydrate, 93.2% fat, 6.4% protein, 6.7 kcal/g), induced changes of gut microbiota and its metabolites, contributing to glucose intolerance but not lipid accumulation in mice. Following a 2-week intervention with KDs, mice fed on KD1 displayed symptoms related to obesity, whereas KD2-fed mice exhibited a decrease in body weight but had severe hepatic lipid accumulation and abnormal fatty acid metabolism, while both KDs led to significant glucose intolerance. Compared to the mice fed on a standard chow diet, the conventional mice fed on both KD1 and KD2 had significant shifted gut microbiota, lower levels of short chain fatty acids (SCFAs) and composition alteration of cecal bile acids. By using an antibiotic cocktail (ABX) to deplete most of the gut microbiota in mice, we found the disturbances induced by KDs in lipid metabolism were similar in the ABX-treated mice to their conventional companions, but the disturbances in glucose metabolism were absent in the ABX-treated mice. In conclusion, these findings suggest that ketogenic diets disrupted glucose and lipid metabolism, at least in mice, and highlight the gut microbial culprits associated with KD induced glucose intolerance rather than lipid accumulation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Li, Gong, Wang, Pan, Li and Zhang.)

Objective: The importance of early microbial dysbiosis in later development of obesity and metabolic disorders has been a subject of debate. Here we tested cause and effect in mice., Methods: Germ-free male Swiss Webster mice were colonized in a specific-pathogen-free (SPF) facility at 1 week (1W) and 3 weeks (3W) of age. They were challenged with a high-fat diet and their responses were compared with SPF mice. Gut microbiota was analyzed by 16S rRNA gene sequencing. Moreover, RNA sequencing of the liver was performed on additional 3W and SPF mice on a regular chow diet., Results: There were no significant differences in weight, food consumption, epididymal fat weight, HbA1c levels, and serum insulin and leptin, whereas the early germ-free period resulted in mice with impaired glucose tolerance. Both the 1W and 3W group peaked 56% ( p < 0.05) and 66% ( p < 0.01) higher in blood glucose than the SPF control group, respectively. This was accompanied by a 45% reduction in the level of the anti-inflammatory cytokine IL-10 in the 1W mice ( p < 0.05). There were no differences in the gut microbiota between the groups, indicating that all mice colonized fully after the germ-free period. Marked effects on hepatic gene expression (728 differentially expressed genes with adjusted p < 0.05 and a fold change ± 1.5) suggested a potential predisposition to a higher risk of developing insulin resistance in the 3W group., Conclusions: Lack of microbes early in life had no impact on adiposity but led to insulin resistance and altered liver gene expression related to glucose metabolism in mice. The study strongly supports the notion that microbial signaling to the liver in the beginning of life can alter the host's risk of developing metabolic disorder later in life., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2024 Maria B. B. Ebert et al.)

Excessive body weight is associated with many chronic metabolic diseases and weight loss, so far, remains the gold standard treatment. However, despite tremendous efforts exploring optimal treatments for obesity, many individuals find losing weight and maintaining a healthy body weight difficult. Weight loss is often not sustainable resulting in weight regain and subsequent efforts to lose weight. This cyclic pattern of weight loss and regain is termed "yoyo dieting" and predisposes individuals to obesity and metabolic comorbidities. How yoyo dieting might worsen obesity complications during the weight recurrence phase remains unclear. In particular, there is limited data on the role of the gut microbiome in yoyo dieting. Gut health distress, especially gut inflammation and microbiome perturbation, is strongly associated with metabolic dysfunction and disturbance of energy homeostasis in obesity. In this review, we summarise current evidence of the crosstalk between the gastrointestinal system and energy balance, and the effects of yoyo dieting on gut inflammation and gut microbiota reshaping. Finally, we focus on the potential effects of post-dieting weight loss in improving gut health and identify current knowledge gaps within the field, including gut-derived peptide hormones and their potential suitability as targets to combat weight regain, and how yoyo dieting and associated changes in the microbiome affect the gut barrier and the enteric nervous system, which largely remain to be determined.

Cyclic weight loss and subsequent regain after dieting and non-dieting periods, a phenomenon termed yoyo dieting, places individuals at greater risk of metabolic complications and alters gut microbiome composition. Resistant starch (RS) improves gut health and systemic metabolism. This study aimed to investigate the effect of yoyo dieting and RS on the metabolism and gut microbiome. C57BL/6 mice were assigned to 6 diets for 20 weeks, including control, high fat (HF), yoyo (alternating HF and control diets every 5 weeks), control with RS, HF with RS, and yoyo with RS. Metabolic outcomes and microbiota profiling using 16S rRNA sequencing were examined. Yoyo dieting resulted in short-term weight loss, which led to improved liver health and insulin tolerance but also a greater rate of weight gain compared to continuous HF feeding, as well as a different microbiota profile that was in an intermediate configuration between the control and HF states. Mice fed HF and yoyo diets supplemented with RS gained less weight than those fed without RS. RS supplementation in yoyo mice appeared to shift the gut microbiota composition closer to the control state. In conclusion, yoyo dieting leads to obesity relapse, and increased RS intake reduces weight gain and might help prevent rapid weight regain via gut microbiome restoration.

This single blind placebo-controlled study has as its main objectives to investigate the influence of dark sweet cherries (DSC) consumption on obesity-related dysbiosis, metabolic endotoxemia, and intestinal permeability. Participants (>18 years old, BMI: 30-40 kg m -2 ) consumed 200 mL of DSC juice with 3 g of DSC powder ( n = 19) or a placebo drink ( n = 21) twice per day for 30 days. The gut microbiota abundance was investigated using 16S ribosomal RNA sequencing on fecal DNA. Metabolic endotoxemia was evaluated by measuring lipopolysaccharide-binding protein (LBP) in fasting plasma samples. Intestinal permeability was assessed using the lactulose/mannitol (L/M) test and by measuring regeneration islet-derived protein 4 (REG4), and interleukin-22 (IL-22) mRNA levels in stool samples. Results showed that DSC supplementation decreased the abundance of Anaerostipes hadrus ( p = 0.02) and Blautia ( p = 0.04), whose changes were significant in BMI ≥ 35 participants ( p = 0.004 and p = 0.006, respectively). Additionally, DSC prevented the increase of Alistipes shahii ( p = 0.005) and Bilophila ( p = 0.01) compared to placebo. Notably, DSC intervention favored the abundance of bacteria supporting a healthy gut ecosystem such as Roseburia intestinalis ( p = 0.01), Turicibacter ( p = 0.01), and Bacteroides vulgatus ( p = 0.003) throughout the intervention, along with Clostridium leptum ( p = 0.03) compared to placebo. The LBP, L/M ratio, REG-4 and IL-22 mRNA levels remained unchanged in placebo and cherry groups, implying that participants did not experience alterations in intestinal permeability. These findings highlight the potential gut-health benefits of DSC and encourage future research among individuals with BMI ≥ 35 and increased intestinal permeability.

Obesity is a major global health concern. Studies suggest that the gut microflora may play a role in protecting against obesity. Probiotics, including lactic acid bacteria and Bifidobacterium , have garnered attention for their potential in obesity prevention. However, the effects of Bifidobacterium -fermented products on obesity have not been thoroughly elucidated. Bifidobacterium , which exists in the gut of animals, is known to enhance lipid metabolism. During fermentation, it produces acetic acid, which has been reported to improve glucose tolerance and insulin resistance, and exhibit anti-obesity and anti-diabetic effects. Functional foods have been very popular around the world, and fermented milk is a good candidate for enrichment with probiotics. In this study, we aim to evaluate the beneficial effects of milks fermented with Bifidobacterium strains on energy metabolism and obesity prevention. Three Bifidobacterium strains (Bif-15, Bif-30, and Bif-39), isolated from newborn human feces, were assessed for their acetic acid production and viability in milk. These strains were used to ferment milk. Otsuka-Long-Evans Tokushima Fatty (OLETF) rats administered Bif-15-fermented milk showed significantly lower weight gain compared to those in the water group. The phosphorylation of AMPK was increased and the expression of lipogenic genes was suppressed in the liver of rats given Bif-15-fermented milk. Additionally, gene expression related to respiratory metabolism was significantly increased in the soleus muscle of rats given Bif-15-fermented milk. These findings suggest that milk fermented with the Bifidobacterium strain Bif-15 can improve lipid metabolism and suppress obesity.

With rising global obesity rates, the demand for effective dietary strategies for obesity management has intensified. This study evaluated the potential of kimchi with various probiotics and bioactive compounds as a dietary intervention for high-fat diet (HFD)-induced obesity in rats. Through a comprehensive analysis incorporating global and targeted metabolomics, gut microbiota profiling, and biochemical markers, we investigated the effects of the 12-week kimchi intake on HFD-induced obesity. Kimchi intake modestly mitigated HFD-induced weight gain and remarkably altered gut microbiota composition, steroid hormones, bile acids, and metabolic profiles, but did not reduce adipose tissue accumulation. It also caused significant shifts in metabolomic pathways, including steroid hormone metabolism, and we found substantial interactions between dietary interventions and gut microbiota composition. Although more research is required to fully understand the anti-obesity effects of kimchi, our findings support the beneficial role of kimchi in managing obesity and related metabolic disorders.

SUMMARYThe gut microbiota is a major factor contributing to the regulation of energy homeostasis and has been linked to both excessive body weight and accumulation of fat mass (i.e., overweight, obesity) or body weight loss, weakness, muscle atrophy, and fat depletion (i.e., cachexia). These syndromes are characterized by multiple metabolic dysfunctions including abnormal regulation of food reward and intake, energy storage, and low-grade inflammation. Given the increasing worldwide prevalence of obesity, cachexia, and associated metabolic disorders, novel therapeutic strategies are needed. Among the different mechanisms explaining how the gut microbiota is capable of influencing host metabolism and energy balance, numerous studies have investigated the complex interactions existing between nutrition, gut microbes, and their metabolites. In this review, we discuss how gut microbes and different microbiota-derived metabolites regulate host metabolism. We describe the role of the gut barrier function in the onset of inflammation in this context. We explore the importance of the gut-to-brain axis in the regulation of energy homeostasis and glucose metabolism but also the key role played by the liver. Finally, we present specific key examples of how using targeted approaches such as prebiotics and probiotics might affect specific metabolites, their signaling pathways, and their interactions with the host and reflect on the challenges to move from bench to bedside., Competing Interests: P.D.C. and A.E. are inventors on patent applications dealing with the use of specific bacteria and components in the treatment of different diseases. P.D.C. was co-founder of The Akkermansia Company SA. C.K. and P.D.C. co-founded Enterosys. A.A. is an employee at Enterosys. The other authors declare no competing interests.

Objective: To decipher the mechanisms by which the major human milk oligosaccharide (HMO), 2'-fucosyllactose (2'FL), can affect body weight and fat mass gain on high-fat diet (HFD) feeding in mice. We wanted to elucidate whether 2'FL metabolic effects are linked with changes in intestinal mucus production and secretion, mucin glycosylation and degradation, as well as with the modulation of the gut microbiota, faecal proteome and endocannabinoid (eCB) system., Results: 2'FL supplementation reduced HFD-induced obesity and glucose intolerance. These effects were accompanied by several changes in the intestinal mucus layer, including mucus production and composition, and gene expression of secreted and transmembrane mucins, glycosyltransferases and genes involved in mucus secretion. In addition, 2'FL increased bacterial glycosyl hydrolases involved in mucin glycan degradation. These changes were linked to a significant increase and predominance of bacterial genera Akkermansia and Bacteroides , different faecal proteome profile (with an upregulation of proteins involved in carbon, amino acids and fat metabolism and a downregulation of proteins involved in protein digestion and absorption) and, finally, to changes in the eCB system. We also investigated faecal proteomes from lean and obese humans and found similar changes observed comparing lean and obese mice., Conclusion: Our results show that the HMO 2'FL influences host metabolism by modulating the mucus layer, gut microbiota and eCB system and propose the mucus layer as a new potential target for the prevention of obesity and related disorders., Competing Interests: Competing interests: PDC is an editor of the journal. PDC is inventor on patent applications dealing with the use bacteria on metabolic disorders. PDC was cofounders of The Akkermansia company SA and Enterosys., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

The gut microbiota is one of the most critical factors in human health. It involves numerous physiological processes impacting host health, mainly via immune system modulation. A balanced microbiome contributes to the gut's barrier function, preventing the invasion of pathogens and maintaining the integrity of the gut lining. Dysbiosis, or an imbalance in the gut microbiome's composition and function, disrupts essential processes and contributes to various diseases. This narrative review summarizes key findings related to the gut microbiota in modern multifactorial inflammatory conditions such as ulcerative colitis or Crohn's disease. It addresses the challenges posed by antibiotic-driven dysbiosis, particularly in the context of C. difficile infections, and the development of novel therapies like fecal microbiota transplantation and biotherapeutic drugs to combat these infections. An emphasis is given to restoration of the healthy gut microbiome through dietary interventions, probiotics, prebiotics, and novel approaches for managing gut-related diseases.

Young people are consuming large amounts of microplastics (MPs) due to the booming development of the take-out industry. To investigate the association between MPs exposure and obesity, 121 volunteers were divided into high MPs exposure (HME) and low MPs exposure (LME) according to the frequency of take-out food consumption. Fecal samples were collected for MPs detection using Raman spectra analysis, and identification of the gut microbiota was based on 16 S rDNA/ITS, while metabolite analysis was performed by LC-MS/MS. High levels of MPs and body mass index (BMI) were observed in the HME group (P < 0.05). Both the multiple linear regression (MLR) model and the binary logistic regression (BLR) (OR: 1.264, 95 % CI: 1.108-1.441, P < 0.001) analysis showed a positive correlation between MPs content and BMI. Microbial community analysis revealed that Veillonella, Alistipes and Dothideomycotes (pathogenic fungi) increased in HME participants, whereas Faecalibacterium and Coprococcus decreased. Meanwhile, analysis of stool metabolites showed that vancomycin resistance, selenocompound metabolism and drug metabolism pathways were enhanced in HME participants. These findings indicate that frequent consumption of take-out food may elevate the intake of microplastics, consequently modifying the gut microbiota and metabolites of young adults, and could represent a potential risk factor for obesity., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

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., (© 2024 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.)

Inulin is a plant polysaccharide which, due to its chemical structure, is not digestible by human gut enzymes but by some bacteria of the human microbiota, acting as a prebiotic. Consequently, inulin consumption has been associated with changes in the composition of the intestinal microbiota related to an improvement of the metabolic state, counteracting different obesity-related disturbances. However, the specific mechanisms of action, including bacterial changes, are not exactly known. Here, a bibliographic review was carried out to study the main effects of inulin on human metabolic health, with a special focus on the mechanisms of action of this prebiotic. Inulin supplementation contributes to body weight and BMI control, reduces blood glucose levels, improves insulin sensitivity, and reduces inflammation markers, mainly through the selective favoring of short-chain fatty acid (SCFA)-producer species from the genera Bifidobacterium and Anaerostipes . These SCFAs have been shown to ameliorate glucose metabolism and decrease hepatic lipogenesis, reduce inflammation, modulate immune activity, and improve anthropometric parameters such as body weight or BMI. In conclusion, the studies collected suggest that inulin intake produces positive metabolic effects through the improvement of the intestinal microbiota and through the metabolites produced by its fermentation.

Objectives: The dietary composition is able to rapidly and significantly influence the diversity of the gut microbiome. This article focuses on how various types of diet affect the composition of the gut microbiome and how dietary changes are able to prevent or slow down the development of non-communicable diseases including obesity, type 2 diabetes mellitus, cardiovascular diseases, and low-grade inflammation., Methods: A review in PubMed and a hand search using references in identified articles were performed. Studies published in English from 2000 to 2024 were included., Results: The studies showed the significant effect of diet on the development of non-communicable diseases dependent on the state of the gut microbiota and molecules it produces. The Western diet that continues to gain in popularity for Czech people, leads to dysbiosis and production of bacterial lipopolysaccharide or trimethylamine N-oxide causing systemic chronic inflammation in the body and thus promoting the development of non-communicable diseases., Conclusions: Findings from this review emphasize the importance of healthy eating habits in the prevention of intestinal dysbiosis and still increasing prevalence and incidence of obesity and other non-communicable diseases.

Obesity poses risks to oocyte maturation and embryonic development in mice and humans, linked to gut microbiota dysbiosis and altered host metabolomes. However, it is unclear whether symbiotic gut microbes have a pivotal role in oocyte quality. In mouse models of fecal microbiota transplantation, we demonstrated aberrant meiotic apparatus and impaired maternal mRNA in oocytes, which is coincident with the poor developmental competence of embryos. Using metabolomics profiling, we discovered that the cytosine and cytidine metabolism was disturbed, which could account for the fertility defects observed in the high-fat diet (HFD) recipient mice. Additionally, cytosine and cytidine are closely related with gut microbiota dysbiosis, which is accompanied by a notable reduction of abundance of Christensenellaceae R-7 group in the HFD mice. In summary, our findings provided evidence that modifying the gut microbiota may be of value in the treatment of infertile female individuals with obesity., Competing Interests: Declaration of competing interest The authors have declared no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Microplastics (MPs) have become a global environmental problem, emerging as contaminants with potentially alarming consequences. However, long-term exposure to polystyrene microspheres (PS-MS) and its effects on diet-induced obesity are not yet fully understood., Objectives: We aimed to investigate the effect of PS-MS exposure on high-fat diet (HFD)-induced obesity and underlying mechanisms., Methods: In the present study, C57BL/6J mice were fed a normal diet (ND) or a HFD in the absence or presence of PS-MS via oral administration for 8 wk. Antibiotic depletion of the microbiota and fecal microbiota transplantation (FMT) were performed to assess the influence of PS-MS on intestinal microbial ecology. We performed 16S rRNA sequencing to dissect microbial discrepancies and investigated the dysbiosis-associated intestinal integrity and inflammation in serum., Results: Compared with HFD mice, mice fed the HFD with PS-MS exhibited higher body weight, liver weight, metabolic dysfunction-associated steatotic liver disease (MASLD) activity scores, and mass of white adipose tissue, as well as higher blood glucose and serum lipid concentrations. Furthermore, 16S rRNA sequencing of the fecal microbiota revealed that mice fed the HFD with PS-MS had greater α -diversity and greater relative abundances of Lachnospiraceae , Oscillospiraceae , Bacteroidaceae , Akkermansiaceae , Marinifilaceae , Deferribacteres , and Desulfovibrio , but lower relative abundances of Atopobiaceae , Bifidobacterium , and Parabacteroides . Mice fed the HFD with PS-MS exhibited lower expression of MUC2 mucin and higher levels of lipopolysaccharide and inflammatory cytokines [tumor necrosis factor- α (TNF- α ), interleukin-6 (IL-6), IL-1 β , and IL-17A] in serum. Correlation analyses revealed that differences in the microbial flora of mice exposed to PS-MS were associated with obesity. Interestingly, microbiota-depleted mice did not show the same PS-MS-associated differences in Muc2 and Tjp1 expression in the distal colon, expression of inflammatory cytokines in serum, or obesity outcomes between HFD and HFD + PS-MS. Importantly, transplantation of feces from HFD + PS-MS mice to microbiota-depleted HFD-fed mice resulted in a lower expression of mucus proteins, higher expression of inflammatory cytokines, and obesity outcomes, similar to the findings in HFD + PS-MS mice., Conclusions: Our findings provide a new gut microbiota-driven mechanism for PS-MS-induced obesity in HFD-fed mice, suggesting the need to reevaluate the adverse health effects of MPs commonly found in daily life, particularly in susceptible populations. https://doi.org/10.1289/EHP13913.

Weight gain variation is a great challenge in diet-induced obesity studies since low-gainer animals are of limited experimental value. The inbred C57BL/6 (B6) mice are frequently used models due to their genetic homogeneity and susceptibility to diet-induced obesity (DIO). The aim of this study is to investigate if the gut microbiota (GM) influences the fraction of low weight gainers in DIO studies. A total of 100 male B6 mice (donor population) were fed a high-fat diet for 14 weeks and divided into the study groups high gainer (HG) and low gainer (LG) based on their weight gain. Subsequently, fecal matter transplantation (FMT) was done on germ-free B6 mice with GM from HG and LG donors (FMT population). LG (13.35 ± 2.5 g) and HG (25.52 ± 2.0 g) animals were identified by the weight gain from week 1 to week 12. Interestingly, the start weight of the LG (20.36 ± 1.4 g) and HG (21.59 ± 0.7 g) groups differed significantly. Transplanting LG or HG fecal matter to germ-free mice resulted in significant differences in weight gain between HG and LG, as well as differences in serum leptin levels and epididymal fat pad weight. A clear LG-specific GM composition could not be distinguished by 16S rRNA gene amplicon sequencing. Surprisingly, significantly more fighting was recorded in LG groups of both donor populations and when transplanted to germ-free mice. The HG and LG phenotypes could be transferred to germ-free mice. The increased fighting in the LG group in both studies suggests not only that the tendency to fight can be transferred by FMT in these mice, but also that fighting should be prevented in DIO studies to minimize the number of LG animals., (© 2024 The Author(s). Clinical and Translational Science published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)