Background and objectives: Gut dysbiosis that resulted from the alteration between host-microbe interaction might worsen obesity-induced systemic inflammation. Gut microbiota manipulation by supplementation of prebiotic inulin may reverse metabolic abnormalities and improve obesity. This study aimed to determine whether inulin supplementation improved intestinal microbiota and microbial functional pathways in children with obesity. Methods: Children with obesity whose BMI above median + 2SDs were recruited to a randomized, double-blinded placebo-controlled study. The participants aged 7–15 years were assigned to inulin supplement extracted from Thai Jerusalem artichoke (intervention), maltodextrin (placebo), and dietary fiber advice groups. All participants received similar monthly conventional advice and follow-up for 6 months. Fecal samples were collected for gut microbiome analysis using 16S rRNA sequencing. Phylogenetic Investigation of Communities by Reconstruction of Unobserved States was performed to infer microbial functional pathways. Results: One hundred and forty-three children with available taxonomic and functional pathway abundance profiles were evaluated. A significant increase in alpha-diversity was observed in the inulin group. Inulin supplementation substantially enhanced Bifidobacterium, Blautia, Megasphaera, and several butyrate-producing bacteria, including Agathobacter, Eubacterium coprostanoligenes, and Subdoligranulum, compared to the other groups. The inulin group showed a significant difference in functional pathways of proteasome and riboflavin metabolism. These changes correlated with clinical and metabolic outcomes exclusively in the inulin group. Conclusions: Inulin supplementation significantly promoted gut bacterial diversity and improved gut microbiota dysbiosis in children with obesity. The modulation of functional pathways by inulin suggests its potential to establish beneficial interactions between the gut microbiota and host physiology. Inulin supplementation could be a strategic treatment to restore the balance of intestinal microbiota and regulate their functions in childhood obesity.

Background. Dysbiosis of intestinal microbiota may be linked to pathogenesis of obesity and metabolic disorders. Objective. This study compared the gut microbiome of obese Thai children with that of healthy controls and examined their relationships with host lifestyle, adiposity, and metabolic profiles. Methods. This cross-sectional study enrolled obese children aged 715. Body composition was evaluated using bioelectrical impedance analysis. Stool samples were analyzed by 16S rRNA sequencing using the Illumina MiSeq platform. Relative abundance and alpha- and beta-diversity were compared with normal-weight Thai children from a previous publication using Wilcoxon rank-sum test and ANOSIM. Relationships of gut microbiota with lifestyle activity, body composition, and metabolic profiles were assessed by canonical correlation analysis (CCA) and Spearman correlation. Results. The study enrolled 164 obese children with a male percentage of 59. Mean age was 10.4±2.2 years with a BMI z-score of 3.2±1. The abundance of Bacteroidetes and Actinobacteria were found to be lower in obese children compared to nonobese children. Alpha-diversity indices showed no differences between groups, while beta-diversity revealed significant differences in the family and genus levels. CCA revealed significant correlations of the relative abundance of gut microbial phyla with sedentary lifestyle and certain metabolic markers. Univariate analysis revealed that Actinobacteria and Bifidobacterium were positively correlated with HDL-C and negatively correlated with body weight and screen time. Additionally, Actinobacteria was also negatively associated with fasting insulin and HOMA-IR. Lactobacillus showed positive correlation with acanthosis nigricans and adiposity. Cooccurrence analysis revealed 90 significant bacterial copresence and mutual exclusion interactions among 43 genera in obese children, whereas only 2 significant cooccurrences were found in nonobese children. Conclusions. The composition and diversity of gut microbiota in obese Thai children were different from those of their normal-weight peers. Specific gut microbiota were associated with lifestyle, adiposity, and metabolic features in obese children. An interventional study is needed to support causality between specific gut microbiota and obesity.

Gut microbiota manipulation may reverse metabolic abnormalities in obesity. Our previous studies demonstrated that inulin supplementation significantly promoted Bifidobacterium and fat-free mass in obese children. We aimed to study gut-muscle axis from inulin supplementation in these children. In clinical phase, the plasma samples from 46 participants aged 7–15 years, were analyzed for muscle biomarkers before and after 6-month inulin supplementation. In parallel, the plausible mechanism of muscle production via gut-muscle axis was examined using macrophage cell line. Bifidobacterium was cultured in semi-refined medium with inulin used in the clinical phase. Cell-free supernatant was collected and used in lipopolysaccharide (LPS)-induced macrophage cell line to determine inflammatory and anti-inflammatory gene expression. In clinical phase, IL-15 and creatinine/cystatin C ratio significantly increased from baseline to the 6th month. In vitro study showed that metabolites derived from Bifidobacterium capable of utilizing inulin contained the abundance of SCFAs. In the presence of LPS, treatment from Bifidobacterium + inulin downregulated TNF-α, IL-6, IL-1β, and iNOS, but upregulated FIZZ-1 and TGF-β expression. Inulin supplementation promoted the muscle biomarkers in agreement with fat-free mass gain, elucidating by Bifidobacterium metabolites derived from inulin digestion showed in vitro anti-inflammatory activity and decreased systemic pro-inflammation, thus promoting muscle production via gut-muscle axis response.Clinical Trial Registry number: NCT03968003.

Background: Obesity is associated with dysbiosis, contributing to inflammation and insulin resistance. Inulin might reduce inflammation by manipulating intestinal microbiota. Objective: We aimed to determine the effects of inulin supplementation on inflammation and assess the relationships of inflammatory cytokines with adiposity and insulin resistance in obese Thai children. Design: Obese Thai children ages 7–15 years were randomly assigned to inulin (intervention), maltodextrin (placebo), and dietary fiber advice groups. All participants received monthly follow-up and identical advice on lifestyle modification for six visits. Body composition was evaluated using bioelectrical impedance analysis. IL-1β, IL-6, TNF-α, and fecal calprotectin were analyzed by ELISA technique at baseline and the final visit. Spearman correlation was used to assess the associations between inflammation and other clinical outcome variables. Results: A total of 155 obese children completed the study (mean age: 10.4 ± 2.2 years, 59% male). All groups showed a significant decrease in BMI z-score, fat mass index (FMI), percent body fat, and trunk FMI. A generalized estimating equation (GEE) model showed significantly decreased IL-1β and TNF-α of 34.8% and 25.8%, (p < 0.0001) but increased IL-6 (21.5%, p = 0.006) in all groups. There were no significant differences in inflammatory cytokines and fecal calprotectin between groups. Mean IL-6 was higher in obese children with acanthosis nigricans (p = 0.048). Only IL-6 was positively correlated with body fat percentage and FMI (r = 0.29, p = 0.008 and r = 0.25, p = 0.049, respectively). Conclusions: Intensive behavioral modification and frequent follow-up visits were effective methods to reduce BMI and adiposity leading to decreased inflammatory cytokines. The additional benefits of inulin on inflammation could not be demonstrated due to the Hawthorne effect. Among the three cytokines, IL-6 was the most likely mediator relating FM and insulin resistance at baseline; therefore, it could be used as a surrogate marker of inflammation in obese children who are at risk for insulin resistance and metabolic syndrome.

Introduction. Obesity is a major threat to public health. Eating behavior and dietary intake of especially high energy-dense food with low nutrients contribute to the current epidemic of childhood obesity. However, the relationship between eating behavior and body composition has yet to be examined in Thai children and adolescents with obesity. We assessed the association between children’s eating behaviors and their body composition in prerandomized patients who participated in the randomized trial titled “Impact of Dietary Fiber as Prebiotics on Intestinal Microbiota in Obese Thai Children”. Methods. During the prerandomization process, a cross-sectional study was conducted. We recruited children and adolescents aged 7 to 15 years from Bangkok, Thailand. Eating behaviors were assessed by the Children’s Eating Behavior Questionnaire (CEBQ), which is a parent or self-reported research instrument conducted by face-to-face interviews. Body mass index (BMI), BMI-for-age Z-score, waist and hip circumferences, and body compositions were assessed. Pearson’s correlation coefficients were used to assess associations between the study variables. Results. Ninety-seven Thai children and adolescents with obesity participated in the study; 59 (61%) were male. Median [IQR] of age and BMI z-score were 10.5 [9.0, 12.2] years and 3.0 [2.6, 3.7], respectively. Subscale for Enjoyment of Food had the highest score. There were no associations between eating behaviors and BMI z-score. However, Emotional Overeating was associated with fat-free mass index (correlation coefficient = 0.24, ) and girls with obesity had lower scores in “Slowness in Eating” compared to boys [mean 2.1 versus 1.8, 95% CI: (−0.06, −0.01), ]. Conclusion. Among Thai children and adolescents with obesity, the difference in multidimensional eating behavior might be affected by fat-free mass. Additional study with a larger sample size needed to explore underlying mechanisms and findings can be used to develop future behavior modification program.

Menkes disease (MD) is an X linked recessive multi-systemic disorder of copper metabolism, resulting from an ATP7A gene mutation. We report a male infant aged 4 months who presented with kinky hair, hypopigmented skin, epilepsy and delayed development. Magnetic resonance imaging (MRI) of brain demonstrated multiple tortuosities of intracranial vessels and brain atrophy. Investigation had showed markedly decreased serum copper and ceruloplasmin. The novel c.2172+1G>T splice-site mutation in the ATP7A gene confirmed MD. He was treated with subcutaneous administration of locally prepared copper-histidine (Cu-His). Following the therapy, hair manifestation was restored and serum ceruloplasmin was normalised 1 month later. Despite the treatment, epilepsy, neurodevelopment and osteoporosis still progressed. He died from severe respiratory tract infection at the age of 9.5 months. These findings suggest that the benefit of Cu-His in our case is limited which might be related to severe presentations and degree of ATP7A mutation.