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1.
Gut Microbes ; 16(1): 2351620, 2024.
Article in English | MEDLINE | ID: mdl-38738766

ABSTRACT

Gut microbiota plays an essential role in nonalcoholic fatty liver disease (NAFLD). However, the contribution of individual bacterial strains and their metabolites to childhood NAFLD pathogenesis remains poorly understood. Herein, the critical bacteria in children with obesity accompanied by NAFLD were identified by microbiome analysis. Bacteria abundant in the NAFLD group were systematically assessed for their lipogenic effects. The underlying mechanisms and microbial-derived metabolites in NAFLD pathogenesis were investigated using multi-omics and LC-MS/MS analysis. The roles of the crucial metabolite in NAFLD were validated in vitro and in vivo as well as in an additional cohort. The results showed that Enterococcus spp. was enriched in children with obesity and NAFLD. The patient-derived Enterococcus faecium B6 (E. faecium B6) significantly contributed to NAFLD symptoms in mice. E. faecium B6 produced a crucial bioactive metabolite, tyramine, which probably activated PPAR-γ, leading to lipid accumulation, inflammation, and fibrosis in the liver. Moreover, these findings were successfully validated in an additional cohort. This pioneering study elucidated the important functions of cultivated E. faecium B6 and its bioactive metabolite (tyramine) in exacerbating NAFLD. These findings advance the comprehensive understanding of NAFLD pathogenesis and provide new insights for the development of microbe/metabolite-based therapeutic strategies.


Subject(s)
Enterococcus faecium , Gastrointestinal Microbiome , Non-alcoholic Fatty Liver Disease , Tyramine , Non-alcoholic Fatty Liver Disease/microbiology , Non-alcoholic Fatty Liver Disease/metabolism , Animals , Humans , Enterococcus faecium/metabolism , Mice , Child , Tyramine/metabolism , Male , Female , Mice, Inbred C57BL , Liver/metabolism , Liver/microbiology , Pediatric Obesity/microbiology , Pediatric Obesity/metabolism , Bacteria/metabolism , Bacteria/classification , Bacteria/genetics , Bacteria/isolation & purification
2.
World J Gastroenterol ; 30(16): 2249-2257, 2024 Apr 28.
Article in English | MEDLINE | ID: mdl-38690025

ABSTRACT

BACKGROUND: This study aimed to identify characteristic gut genera in obese and normal-weight children (8-12 years old) using 16S rDNA sequencing. The research aimed to provide insights for mechanistic studies and prevention strategies for childhood obesity. Thirty normal-weight and thirty age- and sex-matched obese children were included. Questionnaires and body measurements were collected, and fecal samples underwent 16S rDNA sequencing. Significant differences in body mass index (BMI) and body-fat percentage were observed between the groups. Analysis of gut microbiota diversity revealed lower α-diversity in obese children. Di-fferences in gut microbiota composition were found between the two groups. Prevotella and Firmicutes were more abundant in the obese group, while Bacteroides and Sanguibacteroides were more prevalent in the control group. AIM: To identify the characteristic gut genera in obese and normal-weight children (8-12-year-old) using 16S rDNA sequencing, and provide a basis for subsequent mechanistic studies and prevention strategies for childhood obesity. METHODS: Thirty each normal-weight, 1:1 matched for age and sex, and obese children, with an obese status from 2020 to 2022, were included in the control and obese groups, respectively. Basic information was collected through questionnaires and body measurements were obtained from both obese and normal-weight children. Fecal samples were collected from both groups and subjected to 16S rDNA sequencing using an Illumina MiSeq sequencing platform for gut microbiota diversity analysis. RESULTS: Significant differences in BMI and body-fat percentage were observed between the two groups. The Ace and Chao1 indices were significantly lower in the obese group than those in the control group, whereas differences were not significant in the Shannon and Simpson indices. Kruskal-Wallis tests indicated significant differences in unweighted and weighted UniFrac distances between the gut microbiota of normal-weight and obese children (P < 0.01), suggesting substantial disparities in both the species and quantity of gut microbiota between the two groups. Prevotella, Firmicutes, Bacteroides, and Sanguibacteroides were more abundant in the obese and control groups, respectively. Heatmap results demonstrated significant differences in the gut microbiota composition between obese and normal-weight children. CONCLUSION: Obese children exhibited lower α-diversity in their gut microbiota than did the normal-weight children. Significant differences were observed in the composition of gut microbiota between obese and normal-weight children.


Subject(s)
Body Mass Index , Feces , Gastrointestinal Microbiome , Pediatric Obesity , RNA, Ribosomal, 16S , Humans , Pediatric Obesity/microbiology , Pediatric Obesity/diagnosis , Child , RNA, Ribosomal, 16S/genetics , Male , Female , Feces/microbiology , Case-Control Studies , Bacteria/genetics , Bacteria/isolation & purification , Bacteria/classification , DNA, Bacterial/isolation & purification , DNA, Bacterial/analysis , DNA, Bacterial/genetics
3.
Sci Rep ; 12(1): 3140, 2022 02 24.
Article in English | MEDLINE | ID: mdl-35210542

ABSTRACT

Childhood obesity is a risk factor for numerous health conditions. A critical factor in the etiology of obesity appears to be the gut microbiota, which is the microbial community that resides in the human gut. The ratio of the phyla Firmicutes and Bacteroidetes (F/B) and gut bacterial genera that produce short-chain fatty acids (SCFA) have been suggested to contribute to obesity. The current study investigated (1) whether differences in F/B ratio can be observed in infancy and childhood in relation to zBMI in healthy children, and (2) whether an innovative proxy measure adds evidence to a relationship between SCFA producers and the etiology of obesity. Stool samples were collected at five time points, and zBMI was assessed at eight time points throughout the first 12 years of life. Our confirmatory analyses with Bayesian multilevel models showed no relationship between the F/B ratio and zBMI. Also, a proxy measure constructed from known SCFA producers was unrelated to zBMI throughout the first 12 years of life. Exploratory analyses using multilevel and random forest models suggest that the relative abundances of Firmicutes and Bacteroidetes were independently negatively associated with zBMI from infancy through childhood, and the SCFA producing genera Subdoligranulum and Alistipes were negatively related to future BMI in childhood.


Subject(s)
Bacteroidetes , Body Mass Index , Child Development , Fatty Acids, Volatile/metabolism , Firmicutes , Gastrointestinal Microbiome , Pediatric Obesity/microbiology , Bacteroidetes/classification , Bacteroidetes/growth & development , Child , Child, Preschool , Female , Firmicutes/classification , Firmicutes/growth & development , Humans , Infant , Infant, Newborn , Longitudinal Studies , Male
4.
Nutrients ; 14(2)2022 Jan 06.
Article in English | MEDLINE | ID: mdl-35057422

ABSTRACT

Integrated data from molecular and improved culturomics studies might offer holistic insights on gut microbiome dysbiosis triggered by xenobiotics, such as obesity and metabolic disorders. Bisphenol A (BPA), a dietary xenobiotic obesogen, was chosen for a directed culturing approach using microbiota specimens from 46 children with obesity and normal-weight profiles. In parallel, a complementary molecular analysis was carried out to estimate the BPA metabolising capacities. Firstly, catalogues of 237 BPA directed-cultured microorganisms were isolated using five selected media and several BPA treatments and conditions. Taxa from Firmicutes, Proteobacteria, and Actinobacteria were the most abundant in normal-weight and overweight/obese children, with species belonging to the genera Enterococcus, Escherichia, Staphylococcus, Bacillus, and Clostridium. Secondly, the representative isolated taxa from normal-weight vs. overweight/obese were grouped as BPA biodegrader, tolerant, or resistant bacteria, according to the presence of genes encoding BPA enzymes in their whole genome sequences. Remarkably, the presence of sporobiota and concretely Bacillus spp. showed the higher BPA biodegradation potential in overweight/obese group compared to normal-weight, which could drive a relevant role in obesity and metabolic dysbiosis triggered by these xenobiotics.


Subject(s)
Benzhydryl Compounds/adverse effects , Dietary Exposure/adverse effects , Gastrointestinal Microbiome/genetics , Pediatric Obesity/microbiology , Phenols/adverse effects , Xenobiotics/adverse effects , Actinobacillus/drug effects , Case-Control Studies , Child , Dysbiosis/microbiology , Female , Firmicutes/drug effects , Humans , Male , Phenotype , Proteobacteria/drug effects
5.
Curr Med Sci ; 42(1): 210-216, 2022 Feb.
Article in English | MEDLINE | ID: mdl-34985609

ABSTRACT

OBJECTIVE: Childhood obesity is a major health concern worldwide. Previous studies have explored the relationship between obesity and gut microbiota. However, the results from such studies remain contradictory. METHODS: In the present nested case-control study, based on a twin birth cohort study, the relationship between gut microbiota diversity and overweight/obesity in 1- and 6-month-old infants was explored. Twins were enrolled when one child had normal weight and the other child was overweight/obese at six months old. For both infants, stool samples were collected at 1 and 6 months of age. Finally, 12 twins were enrolled in the study. The gut microbiota was identified by 16S rRNA gene sequencing in the V3-V4 area. Six of the twins were monozygotic. RESULTS: The results revealed that the microbiota communities of monozygotic twins were similar to those of dizygotic twins. The relative abundance (RA) of microbiota of 1-month-old twins was significantly higher than that of 6-month-old twins. However, the microbiota diversity of 1-month-old twins was significantly lower than that of 6-month-old twins. In addition, 6-month-old twins had significantly higher RA levels of Bifidobacterium and Lachnospiracea incertae sedis than 1-month-old twins. The 6-month-old group had significantly lower RA levels of Veillonella, Klebsiella, Akkermansia, Streptococcus, or Staphylococcus than the 1-month-old group. At six months, the RA level of Clostridium sensu stricto was higher in the overweight/obesity group than the normal-weight group. CONCLUSION: These findings imply that changes in gut microbiota diversity during infancy may contribute to the development of obesity in early infancy.


Subject(s)
Gastrointestinal Microbiome , Overweight/microbiology , Pediatric Obesity/microbiology , Birth Cohort , Case-Control Studies , Female , Humans , Infant , Male , RNA, Ribosomal, 16S
6.
Nutrients ; 13(11)2021 Oct 21.
Article in English | MEDLINE | ID: mdl-34835958

ABSTRACT

As the very low-calorie ketogenic diet (VLCKD) gains increased interest as a therapeutic approach for many diseases, little is known about its therapeutic use in childhood obesity. Indeed, the role of VLCKD during pregnancy and lactation in influencing short chain fatty acid (SCFA)-producing bacteria and the potential mechanisms involved in the protective effects on obesity are still unclear. Infants are characterized by a diverse gut microbiota composition with higher abundance of SCFA-producing bacteria. Maternal VLCKD during pregnancy and lactation stimulates the growth of diverse species of SCFA-producing bacteria, which may induce epigenetic changes in infant obese gene expression and modulate adipose tissue inflammation in obesity. Therefore, this review aims to determine the mechanistic role of SCFAs in mediating VLCKD-infant gut microbiota relationships and its protective effects on obesity.


Subject(s)
Caloric Restriction , Diet, Ketogenic , Fatty Acids, Volatile/metabolism , Gastrointestinal Microbiome , Pediatric Obesity/microbiology , Epigenesis, Genetic , Humans , Infant , Pediatric Obesity/genetics
7.
Gut Microbes ; 13(1): 1960135, 2021.
Article in English | MEDLINE | ID: mdl-34491882

ABSTRACT

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.


Subject(s)
Bacteria/metabolism , Diabetes Mellitus, Type 2/pathology , Gastrointestinal Microbiome/physiology , Metabolic Syndrome/microbiology , Pediatric Obesity/microbiology , Bacteria/classification , Child , Dysbiosis , Feeding Behavior , Humans
8.
Clin Nutr ; 40(7): 4585-4594, 2021 07.
Article in English | MEDLINE | ID: mdl-34229263

ABSTRACT

BACKGROUND & AIMS: Variations in gut microbiota might impact metabolism leading to body weight excess. We assessed the impact of a probiotic supplementation in pediatric obesity on weight, metabolic alterations, selected gut microbial groups, and functionality. METHODS: Cross-over, double-blind, randomized control trial (BIFI-OBESE trial; NCT03261466). 101 youths (6-18 years, Tanner stage ≥2) with obesity and insulin-resistance on diet were randomized to 2 × 109 CFU/AFU/day of Bifidobacterium breve BR03 (DSM 16604) and B. breve B632 (DSM 24706) (51) or placebo (50) for 8 weeks with a 4-weeks wash-out period. RESULTS: All subjects (M/F 54/47) completed the first 8 weeks, and 82 (M/F 43/39) the last part without adverse events. Mixed-effects models revealed a carry-over effect on many variables in the entire study, narrowing the analysis to the first 8 weeks before the wash-out periods. All subjects improved metabolic parameters, and decreased weight and Escherichia coli counts. Probiotics improved insulin sensitivity at fasting (QUICKI, 0.013 CI95%0.0-0.03) and during OGTT (ISI, 0.654 CI95%-0.11-1.41). Cytokines, GLP1, and target microbial counts did not vary. Of 25 SCFAs, acetic acid and acetic acid pentyl-ester relative abundance remained stable in the probiotics, while increased in the placebo (p < 0.02). A signature of five butanoic esters identified three clusters, one of them had better glucose responses during probiotics. CONCLUSION: An 8 weeks treatment with B. breve BR03 and B632 had beneficial effects on insulin sensitivity in youths with obesity. Microbiota functionality could influence metabolic answers to probiotics. Long-term studies to confirm and enrich our findings are justified. Tailored probiotic treatments could be an additional strategy for obesity. TRIAL REGISTRATION: NCT03261466.


Subject(s)
Bifidobacterium breve , Gastrointestinal Microbiome/physiology , Insulin Resistance , Pediatric Obesity/physiopathology , Probiotics/administration & dosage , Adolescent , Child , Cross-Over Studies , Double-Blind Method , Female , Humans , Insulin/blood , Male , Pediatric Obesity/microbiology , Pediatric Obesity/therapy , Treatment Outcome
9.
PLoS One ; 16(3): e0247378, 2021.
Article in English | MEDLINE | ID: mdl-33765008

ABSTRACT

Characterization of metabolites and microbiota composition from human stool provides powerful insight into the molecular phenotypic difference between subjects with normal weight and those with overweight/obesity. The aim of this study was to identify potential metabolic and bacterial signatures from stool that distinguish the overweight/obesity state in children/adolescents. Using 1H NMR spectral analysis and 16S rRNA gene profiling, the fecal metabolic profile and bacterial composition from 52 children aged 7 to 16 was evaluated. The children were classified into three groups (16 with normal-weight, 17 with overweight, 19 with obesity). The metabolomic analysis identified four metabolites that were significantly different (p < 0.05) among the study groups based on one-way ANOVA testing: arabinose, butyrate, galactose, and trimethylamine. Significantly different (p < 0.01) genus-level taxa based on edgeR differential abundance tests were genus Escherichia and Tyzzerella subgroup 3. No significant difference in alpha-diversity was detected among the three study groups, and no significant correlations were found between the significant taxa and metabolites. The findings support the hypothesis of increased energy harvest in obesity by human gut bacteria through the growing observation of increased fecal butyrate in children with overweight/obesity, as well as an increase of certain monosaccharides in the stool. Also supported is the increase of trimethylamine as an indicator of an unhealthy state.


Subject(s)
Feces/microbiology , Obesity/microbiology , Pediatric Obesity/microbiology , Adolescent , Bacteria/genetics , Child , Czech Republic/epidemiology , Female , Gastrointestinal Microbiome/genetics , Humans , Male , Metabolome , Metabolomics , Obesity/metabolism , Pediatric Obesity/metabolism , Proton Magnetic Resonance Spectroscopy , RNA, Ribosomal, 16S/genetics
10.
Obesity (Silver Spring) ; 29(3): 569-578, 2021 03.
Article in English | MEDLINE | ID: mdl-33624438

ABSTRACT

OBJECTIVE: The purpose of this study was to establish a biorepository of clinical, metabolomic, and microbiome samples from adolescents with obesity as they undergo lifestyle modification. METHODS: A total of 223 adolescents aged 10 to 18 years with BMI ≥95th percentile were enrolled, along with 71 healthy weight participants. Clinical data, fasting serum, and fecal samples were collected at repeated intervals over 6 months. Herein, the study design, data collection methods, and interim analysis-including targeted serum metabolite measurements and fecal 16S ribosomal RNA gene amplicon sequencing among adolescents with obesity (n = 27) and healthy weight controls (n = 27)-are presented. RESULTS: Adolescents with obesity have higher serum alanine aminotransferase, C-reactive protein, and glycated hemoglobin, and they have lower high-density lipoprotein cholesterol when compared with healthy weight controls. Metabolomics revealed differences in branched-chain amino acid-related metabolites. Also observed was a differential abundance of specific microbial taxa and lower species diversity among adolescents with obesity when compared with the healthy weight group. CONCLUSIONS: The Pediatric Metabolism and Microbiome Study (POMMS) biorepository is available as a shared resource. Early findings suggest evidence of a metabolic signature of obesity unique to adolescents, along with confirmation of previously reported findings that describe metabolic and microbiome markers of obesity.


Subject(s)
Pediatric Obesity/metabolism , Pediatric Obesity/microbiology , Adolescent , Body Weight/physiology , Case-Control Studies , Child , Fasting , Feces/microbiology , Female , Gastrointestinal Microbiome/genetics , Gastrointestinal Microbiome/physiology , Humans , Male , Metabolomics/methods , Preliminary Data , RNA, Ribosomal, 16S/analysis , RNA, Ribosomal, 16S/genetics
11.
Gut Microbes ; 13(1): 1-15, 2021.
Article in English | MEDLINE | ID: mdl-33596768

ABSTRACT

Obesity is a growing worldwide problem that generally starts in the early years of life and affects minorities more often than Whites. Thus, there is an urgency to determine factors that can be used as targets as indicators of obesity. In this study, we attempt to generate a profile of gut and oral microbial clades predictive of disease status in African American (AA) and European American (EA) children. 16S rDNA sequencing of the gut and saliva microbial profiles were correlated with salivary amylase, socioeconomic factors (e.g., education and family income), and obesity in both ethnic populations. Gut and oral microbial diversity between AA and EA children showed significant differences in alpha-, beta-, and taxa-level diversity. While gut microbial diversity between obese and non-obese was not evident in EA children, the abundance of gut Klebsiella and Magasphaera was associated with obesity in AA children. In contrast, an abundance of oral Aggregatibacter and Eikenella in obese EA children was observed. These observations suggest an ethnicity-specific association with gut and oral microbial profiles. Socioeconomic factors influenced microbiota in obesity, which were ethnicity dependent, suggesting that specific approaches to confront obesity are required for both populations.


Subject(s)
Microbiota , Pediatric Obesity/ethnology , Pediatric Obesity/microbiology , Black or African American , Child , DNA Copy Number Variations , Female , Gastrointestinal Microbiome , Health Status Disparities , Humans , Male , Saliva/enzymology , Saliva/microbiology , Salivary alpha-Amylases/genetics , Socioeconomic Factors , White People
12.
Pediatr Obes ; 16(5): e12741, 2021 05.
Article in English | MEDLINE | ID: mdl-33089672

ABSTRACT

BACKGROUND: Increased intestinal permeability may be associated with certain disorders, such as obesity and small intestine bacterial overgrowth (SIBO). OBJECTIVE: This study aimed to investigate intestinal permeability and SIBO in excess weight adolescents. METHODS: This cross-sectional study included 67 adolescents with excess weight and 66 normal weight adolescents. Excess weight was defined as a body mass index for age (BMI/age) > +1 SD, which includes having excess body weight and obesity. SIBO was diagnosed by a breath test after the ingestion of lactulose according to the production of hydrogen and methane. Zonulin (haptoglobin) was considered an indicator of intestinal permeability. RESULTS: Adolescents with excess weight had a higher height/age Z-score (median [25th; 75th percentile]: +0.6 [-0.4; +1.0]) than those in the normal weight group (-0.1 [-0.6; +0.7]; P = .014). Zonulin (mg/mL) in the excess weight (2.3 [1.5; 3.8]) adolescents was higher than that in the normal weight (1.6 [1.0; 2.2]) adolescents (P < .001). SIBO was diagnosed in 23.3% (31/133) of the adolescents. The adolescents with SIBO had a lower (P < .05) BMI/age (+0.6 [-0.6; +1.9]) and height/age (-0.3 [-0.7; +0.3]) than the adolescents without SIBO (+1.3 [+0.1; +2.6] and +0.2 [-0.5; +1.0], respectively). No association was found between zonulin and SIBO. CONCLUSION: Excess weight is associated with increased intestinal permeability. No relationship was found between SIBO and intestinal permeability; however, SIBO was related to lower BMI and height for age Z-scores.


Subject(s)
Intestine, Small , Lactulose , Overweight/microbiology , Pediatric Obesity/microbiology , Adolescent , Blind Loop Syndrome , Breath Tests , Case-Control Studies , Cross-Sectional Studies , Humans , Intestine, Small/microbiology , Permeability
13.
Pediatr Obes ; 16(5): e12748, 2021 05.
Article in English | MEDLINE | ID: mdl-33191616

ABSTRACT

BACKGROUND: The association of gut microbiota with obesity and its cardio-metabolic complications in paediatric populations is still controversial. OBJECTIVE: We investigated the association of obesity and cardio-metabolic traits with gut microbiota on 167 and 163 children with normal weight and obesity from Mexico City and Oaxaca, Mexico. METHODS: Anthropometric and biochemical traits were measured. The microbial communities were determined by high-throughput sequencing of bacterial 16S rRNA gene v3-v4 region. RESULTS: The gut microbial community structure was associated with obesity and fasting plasma insulin (FPI) in Mexico City (PObesity = 0.012, PFPI = 0.0003) and Oaxaca (PObesity = 0.034, PFPI = 0.016), and with triglycerides (TG) in Oaxaca (P = .0002). The Firmicutes/Bacteroidetes ratio was positively associated with TG in Oaxaca (P = .003). Firmicutes and Bacteroidetes phyla were positively and negatively associated with obesity (Mexico City: PFirmicutes = 0.013, PBacteroidetes = 0.009) and TG (Oaxaca: PFirmicutes = 0.002, PBacteroidetes = 0.004). In Oaxaca, Verrucomicrobia was negatively associated with obesity (P = .004). In Mexico City, the bacterial genus Fusicatenibacter, Romboutsia, Ruminococcaceae, Ruminiclostridium, Blautia, Clostridium, Anaerostipes and Intestinibacter were associated with obesity and FPI, while in Oaxaca, Bacteroides, Alistipes and Clostridium were associated with TG. CONCLUSION: The gut microbial community structure in children is associated with obesity and FPI in Mexico City, and with obesity, FPI and TG in Oaxaca.


Subject(s)
Gastrointestinal Microbiome , Insulin/blood , Pediatric Obesity/epidemiology , Triglycerides/blood , Child , Fasting , Humans , Mexico/epidemiology , Pediatric Obesity/microbiology , RNA, Ribosomal, 16S/genetics
14.
Biomed Pharmacother ; 134: 111117, 2021 Feb.
Article in English | MEDLINE | ID: mdl-33360047

ABSTRACT

BACKGROUND: Metformin, a first-line oral antidiabetic agent that has shown promising results in terms of treating childhood and adolescent obesity, might influence the composition of the gut microbiota. We aimed to evaluate whether the gut microbiota of non-diabetic children with obesity changes after a metformin intervention. METHODS: The study was a multicenter and double-blind randomized controlled trial in 160 children with obesity. Children were randomly assigned to receive either metformin (1 g/day) or placebo for 6 months in combination with healthy lifestyle recommendations in both groups. Then, we conducted a metagenomic analysis in a subsample obtained from 33 children (15 metformin, 18 placebo). A linear mixed-effects model (LMM) was used to determine the abundance changes from baseline to six months according to treatment. To analyze the data by clusters, a principal component analysis was performed to understand whether lifestyle habits have a different influence on the microbiota depending on the treatment group. RESULTS: Actinobacteria abundance was higher after placebo treatment compared with metformin. However, the interaction time x treatment just showed a trend to be significant (4.6% to 8.1% after placebo vs. 3.8 % to 2.6 % after metformin treatment, p = 0.055). At genus level, only the abundance of Bacillus was significantly higher after the placebo intervention compared with metformin (2.5% to 5.7% after placebo vs. 1.5 % to 0.8 % after metformin treatment, p = 0.044). Furthermore, different ensembles formed by Firmicutes, Bacteroidetes, and Verrucomicrobia were found according to the interventions under a similar food consumption. CONCLUSION: Further studies with a large sample size controlled by lifestyle patterns are required in obese children and adolescents to clarify whether metformin might trigger gut microbiota alterations. TRIAL REGISTRATION: Registered on the European Clinical Trials Database (EudraCT, ID: 2010-023061-21) on 14 November 2011.


Subject(s)
Bacteria/drug effects , Gastrointestinal Microbiome/drug effects , Hypoglycemic Agents/therapeutic use , Intestines/microbiology , Metagenome , Metagenomics , Metformin/therapeutic use , Pediatric Obesity/drug therapy , Adolescent , Age Factors , Bacteria/genetics , Bacteria/growth & development , Child , Double-Blind Method , Female , Humans , Life Style , Male , Pediatric Obesity/diagnosis , Pediatric Obesity/microbiology , Spain , Time Factors , Treatment Outcome
15.
Gut Microbes ; 13(1): 1-15, 2021.
Article in English | MEDLINE | ID: mdl-33382954

ABSTRACT

Artificial sweetener consumption by pregnant women has been associated with an increased risk of infant obesity, but the underlying mechanisms are unknown. We aimed to determine if maternal consumption of artificially sweetened beverages (ASB) during pregnancy is associated with modifications of infant gut bacterial community composition and function during the first year of life, and whether these alterations are linked with infant body mass index (BMI) at one year of age. We studied 100 infants from the prospective Canadian CHILD Cohort Study, selected based on maternal ASB consumption during pregnancy (50 non-consumers and 50 daily consumers). BMI was higher among ASB-exposed infants. Infant stool (16S rRNA gene sequencing) and urine (untargeted metabolomics) were acquired in early (3-4 months) and late (12 months) infancy. We identified four microbiome clusters, of which two recapitulated the maturation trajectory of the infant gut bacterial communities from immature (Cluster 1) to mature (Cluster 4) and two deviated from this trajectory (Clusters 2 and 3). Maternal ASB consumption did not differ between clusters, but was associated with community-level shifts in infant gut bacterial taxonomy structure and depletion of several Bacteroides sp. in Cluster 2. In the complete dataset, urine succinate and spermidine levels at 3 months were higher in ASB-exposed infants, and urine succinate was positively associated with BMI at one-year-old. Overall, gestational exposure to ASB was associated with gut microbiota structure in infants from Cluster 2, and gut microbiota structure was associated with infant BMI. Gestational exposure to ASB was positively associated with infant urine succinate and spermidine. Succinate was found to mediate 29% of the effect of ASB exposure on BMI at one-year-old, revealing a potential role of this metabolite in increased infant weight linked to gestational ASB consumption. As we face an unprecedented rise in childhood obesity, future studies should evaluate the causal relationships between maternal ASB consumption (a modifiable exposure), gut microbiota and metabolites, infant metabolism, and body composition.


Subject(s)
Artificially Sweetened Beverages/adverse effects , Body Mass Index , Gastrointestinal Microbiome , Prenatal Exposure Delayed Effects/metabolism , Prenatal Exposure Delayed Effects/microbiology , Canada , Female , Humans , Infant , Male , Pediatric Obesity/etiology , Pediatric Obesity/metabolism , Pediatric Obesity/microbiology , Pregnancy , Prenatal Exposure Delayed Effects/etiology , Prenatal Exposure Delayed Effects/urine , Prospective Studies , Spermidine/urine , Succinic Acid/urine
16.
Biomed Res Int ; 2020: 6587136, 2020.
Article in English | MEDLINE | ID: mdl-32908903

ABSTRACT

Emerging data suggest that the gut microbiome is related to the pathophysiology of obesity. This study is aimed at characterizing the gut microbiota composition between obese and normal-weight Korean children aged 5-13. We collected fecal samples from 22 obese and 24 normal-weight children and performed 16S rRNA gene sequencing using the Illumina MiSeq platform. The relative abundance of the phylum Bacteroidetes was lower in the obese group than in the normal-weight group and showed a significant negative correlation with BMI z-score. Linear discriminative analysis (LDA) coupled with effect size measurement (LEfSe) analysis also revealed that the Bacteroidetes population drove the divergence between the groups. There was no difference in alpha diversity, but beta diversity was significantly different between the normal-weight and obese groups. The gut microbial community was linked to BMI z-score; blood biomarkers associated with inflammation and metabolic syndrome; and dietary intakes of niacin, sodium, vitamin B6, and fat. The gut microbiota of the obese group showed more clustering of genera than that of the normal-weight group. Phylogenetic investigation of communities by reconstruction of unobserved states (PICRUSt) analysis revealed that the functions related to carbohydrate and lipid metabolism in the microbiota were more enriched in the normal-weight group than in the obese group. Our data may contribute to the understanding of the gut microbial structure of young Korean children in relation to obesity. These findings suggest that Bacteroidetes may be a potential therapeutic target in pediatric obesity.


Subject(s)
Bacteroidetes/physiology , Gastrointestinal Microbiome/physiology , Pediatric Obesity/microbiology , Adolescent , Bacteroidetes/genetics , Carbohydrates/genetics , Cross-Sectional Studies , Female , Gastrointestinal Microbiome/genetics , Humans , Inflammation/genetics , Inflammation/microbiology , Lipid Metabolism/genetics , Male , Pediatric Obesity/genetics , RNA, Ribosomal, 16S/genetics , Republic of Korea
18.
Exp Mol Med ; 52(7): 1048-1061, 2020 07.
Article in English | MEDLINE | ID: mdl-32624568

ABSTRACT

Childhood obesity has reached epidemic levels and is a serious health concern associated with metabolic syndrome, nonalcoholic fatty liver disease, and gut microbiota alterations. Physical exercise is known to counteract obesity progression and modulate the gut microbiota composition. This study aims to determine the effect of a 12-week strength and endurance combined training program on gut microbiota and inflammation in obese pediatric patients. Thirty-nine obese children were assigned randomly to the control or training group. Anthropometric and biochemical parameters, muscular strength, and inflammatory signaling pathways in mononuclear cells were evaluated. Bacterial composition and functionality were determined by massive sequencing and metabolomic analysis. Exercise reduced plasma glucose levels and increased dynamic strength in the upper and lower extremities compared with the obese control group. Metagenomic analysis revealed a bacterial composition associated with obesity, showing changes at the phylum, class, and genus levels. Exercise counteracted this profile, significantly reducing the Proteobacteria phylum and Gammaproteobacteria class. Moreover, physical activity tended to increase some genera, such as Blautia, Dialister, and Roseburia, leading to a microbiota profile similar to that of healthy children. Metabolomic analysis revealed changes in short-chain fatty acids, branched-chain amino acids, and several sugars in response to exercise, in correlation with a specific microbiota profile. Finally, the training protocol significantly inhibited the activation of the obesity-associated NLRP3 signaling pathway. Our data suggest the existence of an obesity-related deleterious microbiota profile that is positively modified by physical activity intervention. Exercise training could be considered an efficient nonpharmacological therapy, reducing inflammatory signaling pathways induced by obesity in children via microbiota modulation.


Subject(s)
Exercise/physiology , Gastrointestinal Microbiome , Inflammation/microbiology , Pediatric Obesity/metabolism , Pediatric Obesity/microbiology , Pediatric Obesity/physiopathology , Signal Transduction , Case-Control Studies , Child , Endurance Training , Female , Humans , Male , Metabolomics , Pediatric Obesity/blood , Phylogeny , Principal Component Analysis
19.
Obes Res Clin Pract ; 14(3): 271-278, 2020.
Article in English | MEDLINE | ID: mdl-32518007

ABSTRACT

This study examined the association between intestinal lactobacilli and obesity dependent on dietary patterns in children. A cross-sectional study was conducted including 1111 children, 6-12 years old. Obesity was determined according to the WHO cut-off points. Diet information from a Food Frequency Questionnaire identified three dietary patterns. Lactobacillus sp. were determined by a real-time polymerase chain reaction (PCR). The consumption of complex carbohydrates and a high abundance of L. paracasei were associated with a lower risk of obesity (0.35, Confidence Interval 95% 0.19-0.65). The same happened with a medium consumption of fats and a medium abundance of L. paracasei (0.43, CI95% 0.24-0.78). In contrast, an increased risk of obesity is observed with a medium and high consumption of simple carbohydrates (2.37, CI95% 1.29-4.34 and 2.52, CI95% 1.36-4.66, respectively, p-trend<0.05), and low consumption of complex carbohydrates (2.49, CI95% 1.35-4.58), in the presence of a high relative abundance of L. reuteri. A high relative abundance of L. paracasei decreased the risk of obesity, even when high-fat and simple carbohydrate diets were consumed; while a high relative abundance of L. reuteri was associated with a greater possibility of obesity with these types of diets. Our results provide evidence of diet implication in metabolism regulators like lactobacilli. This is helpful in strategies development to promote healthy diets during early stages of life.


Subject(s)
Diet/adverse effects , Dietary Carbohydrates/analysis , Lacticaseibacillus paracasei , Lactobacillus/metabolism , Pediatric Obesity/microbiology , Child , Child Nutritional Physiological Phenomena , Cross-Sectional Studies , Diet/methods , Female , Gastrointestinal Microbiome , Humans , Male , Pediatric Obesity/epidemiology , Protective Factors
20.
Child Obes ; 16(5): 358-366, 2020 07.
Article in English | MEDLINE | ID: mdl-32429742

ABSTRACT

Background: Differences in gut microbiota composition have been associated with obesity and metabolic alterations in children. The aim of this study was to analyze the abundance of the main bacterial families of the gut among children according to their body composition and metabolic markers. Methods: A cross-sectional study was conducted with 93 school-aged children (8.4 ± 1.6 years old). Anthropometric and body composition variables were measured and a blood sample was collected to determine glucose, insulin, lipid profile, C-reactive protein, leptin, and cytokines [interleukin 6, interleukin 10 (IL-10), tumor necrosis factor α (TNFα)]. DNA was extracted from stool samples and the abundance of bacterial families (Bacteroidaceae-Porphyromonadaceae-Prevotellaceae, Lactobacillaceae, Enterococcaceae, and Lachnospiraceae-Ruminococcaceae) was determined by qPCR assays. Results: Children with obesity and high waist/height ratio had lower Bacteroidaceae-Porphyromonadaceae-Prevotellaceae and higher abundance of Lactobacillaceae when compared with normal-weight children. TNFα was negatively associated and IL-10 was positively associated with Bacteroidaceae-Porphyromonadaceae-Prevotellaceae. Triglycerides showed a positive relationship with Lachnospiraceae-Ruminococcaceae whereas high-density lipoprotein-cholesterol was negatively associated with Lactobacillaceae. Conclusion: In rural Mexican school-aged children, a low abundance of Bacteroidaceae-Porphyromonadaceae-Prevotellaceae and a high abundance of Lactobacillaceae are associated with obesity and metabolic disturbances.


Subject(s)
Body Composition , Gastrointestinal Microbiome , Obesity, Abdominal/blood , Pediatric Obesity/microbiology , Apolipoproteins/blood , Biomarkers/blood , Body Mass Index , Child , Cross-Sectional Studies , Cytokines/blood , Female , Humans , Insulin/blood , Male , Mexico , Pediatric Obesity/diagnosis , Risk Factors , Triglycerides/blood
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