Inulin supplementation exhibits increased muscle mass via gut-muscle axis in children with obesity: double evidence from clinical and in vitro studies.

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-1ß, and iNOS, but upregulated FIZZ-1 and TGF-ß 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.

The Impact of Dietary Fiber as a Prebiotic on Inflammation in Children with Obesity.

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-1ß, 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-1ß 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.

Effects of inulin supplementation on body composition and metabolic outcomes in children with obesity.

Inulin might improve body composition in obese children. We aimed to determine the effects of inulin supplementation on body composition and metabolic outcomes in obese children. A randomized, double-blinded placebo-controlled study was conducted in obese Thai children aged 7-15 years. Participants were assigned to 3 treatment groups for 6 months: 13 g of extracted inulin powder from Thai Jerusalem artichoke, isocaloric maltodextrin, and dietary fiber advice groups. Body composition was assessed by bioelectrical impedance analysis. One-hundred and fifty-five children completed the study (mean age 10.4 ± 2.2 years, BMI z-score 3.2 ± 1.0, 59% male). The drop-out rate was 6%. The inulin extract yielded more than 90% compliance without significant gastrointestinal side effects. All three groups demonstrated a significant decrease in BMI z-score, fat mass index (FMI), and trunk FMI, but the differences between groups were not observed. Fat-free mass index significantly increased only in the inulin group (16.18 ± 1.90 vs. 16.38 ± 1.98 kg/m2, P = 0.009). There were no significant differences in the metabolic profiles between groups. Despite showing no substantial effect on adiposity, inulin may increase fat-free mass in obese children. Further research in the change of gut microbiota composition is needed to determine inulin's impact on host-microbe interaction in pediatric obesity.

Association of Human Intestinal Microbiota with Lifestyle Activity, Adiposity, and Metabolic Profiles in Thai Children with 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 7-15. 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.

Copper-histidine therapy in an infant with novel splice-site variant in the ATP7A gene of Menkes disease: the first experience in South East Asia and literature review.

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.

Glycemic index and glycemic load of common fruit juices in Thailand.

BACKGROUND: The glycemic index (GI) reflects body responses to different carbohydrate-rich foods. Generally, it cannot be simply predicted from the composition of the food but needs in vivo testing. METHODS: Healthy adult volunteers with normal body mass index were recruited. Each volunteer was asked to participate in the study center twice in the first week to consume the reference glucose (50 g) and once a week thereafter to consume the study fruit juices in a random order. The study fruit juices were Florida orange juice, Tangerine orange juice, Blackcurrant mixed juice, and Veggie V9 orange carrot juice which were already available on the market. The serving size of each fruit juice was calculated to provide 50 g of glycemic carbohydrate. The fasting and subsequent venous blood samplings were obtained through the indwelling venous catheters at 0, 15, 30, 45, 60, 90, and 120 min after the test drink consumption and immediately sent for plasma glucose and insulin. GI and insulin indices were calculated from the incremental area under the curve of postprandial glucose of the test drink divided by the reference drink. Glycemic load (GL) was calculated from the GI multiplied by carbohydrate content in the serving size. RESULTS: A total of 12 volunteers participated in the study. Plasma glucose and insulin peaked at 30 min after the drink was consumed, and then started to decline at 120 min. Tangerine orange juice had the lowest GI (34.1 ± 18.7) and GL (8.1 g). Veggie V9 had the highest GI (69.6 ± 43.3) but it was in the third GL rank (12.4 g). The insulin responses correlated well with the GI. Fructose to glucose ratio was inversely associated with GI and insulin responses for all study fruit juices. Fiber contents in the study juices did not correlate with glycemic and insulin indices. CONCLUSIONS: The GIs of fruit juices were varied but consistently showed a positive correlation with insulin indices. Fruit juices with low GI are a healthier choice for people with diabetes as well as individuals who want to stay healthy since it produces more subtle postprandial glucose and insulin responses.

Tailoring an online breastfeeding course for Southeast Asian paediatric trainees- A qualitative study of user experience from Malaysia and Thailand.

BACKGROUND: This study explored the user experiences of paediatric postgraduate trainees in Malaysia and Thailand in using a 2 h and 15 min online module for breastfeeding developed for Southeast Asia, which was adapted from existing European online modules for European and German Continuing Medical Education (CME) credits. METHODS: A qualitative study using focus group discussions (FGDs) was conducted with paediatric postgraduate trainees who used an online English-language breastfeeding module in two Thai universities (May 2020, done online) and two Malaysian universities (Sept- Nov 2019, in-person). FGDs explored module usability and utility. Sessions were transcribed verbatim and analysed thematically. The process of coding was done collaboratively by Thai and Malaysian researchers. RESULTS: Twenty Six resident trainees participated (Thai, n = 13; Malaysian, n = 13). Ages ranged from 29-34 years old, with 21 females. Nineteen participants had never used online learning modules prior to this. Participants took between 1 to 5 sessions to complete the breastfeeding module. Four themes emerged from their experience. 1) The online learning module was more engaging and detailed than previous lectures, courses and/or books, but lacked hands-on training. 2) Using an online platform facilitated learning as eased navigation and resource searching, however, problems were encountered navigating the module on some devices. 3) Learners preferred less words and more graphics, as this helped them capture key messages. 4) Regionally tailored content elicited a mixed reaction from participants. CONCLUSIONS: Users found that the adapted module compared favourably with previous learning experiences. However, online learning modules lack hands-on training, and implementation should ideally incorporate a mix of both. Consideration of device diversity and preferences for how content was adapted for local settings are needed for tailoring.

Effects of low-glycemic index diet on plasma adipokines in obese children.

BACKGROUND: A low-glycemic index (GI) diet may modulate adipocyte-produced adipokines linking to insulin resistance. METHODS: The stored plasma samples from the RCT of a low-GI vs. conventional diet in obese children were analyzed for adipokines: leptin, adiponectin, resistin, and visfatin. Their relationships with clinical outcomes were assessed. RESULTS: Fifty-two participants completed the 6-month intervention trial (mean age: 12.0 ± 2.0 years, 35 boys). Both groups had significantly decreased BMI z-scores from baseline whereas the low-GI group had significant reduction in fasting insulin and HOMA-IR. There were no differences in adipokines between the groups before and after the intervention. However, there was an association between baseline leptin and the change of fat mass index (FMI) but not the insulin resistance in both groups. The higher the baseline leptin was, the lower the changes were for FMI after the intervention. CONCLUSION: Despite no demonstrable effect of low-GI diet on plasma adipokines, the higher baseline leptin was correlated with lower reduction of fat mass. Leptin resistance may have a detrimental effect on the reduction of adiposity in obese children. Baseline leptin could be a useful predictor of the change in body composition in an obesity intervention trial. IMPACT: Leptin resistance may have a detrimental effect in reducing the adiposity in obese children. This study is the first of its kind to compare the plasma adipokine concentrations of obese children on low-GI diet and conventional diet. We found that serum leptin was significantly correlated with the reduction of BMI z-score and FMI in both groups. Baseline leptin could be a useful predictor of the change in body composition in an obesity intervention trial.

Immunomodulation of dendritic cells by Lactobacillus reuteri surface components and metabolites.

BACKGROUND: Lactic acid bacteria are commensal members of the gut microbiota and are postulated to promote host health. Secreted factors and cell surface components from Lactobacillus species have been shown to modulate the host immune system. However, the precise role of L. reuteri secreted factors and surface proteins in influencing dendritic cells (DCs) remains uncharacterized. HYPOTHESIS: We hypothesize that L. reuteri secreted factors will promote DC maturation, skewing cells toward an anti-inflammatory phenotype. In acute colitis, we speculate that L. reuteri promotes IL-10 and dampens pro-inflammatory cytokine production, thereby improving colitis. METHODS & RESULTS: Mouse bone marrow-derived DCs were differentiated into immature dendritic cells (iDCs) via IL-4 and GM-CSF stimulation. iDCs exposed to L. reuteri secreted factors or UV-irradiated bacteria exhibited greater expression of DC maturation markers CD83 and CD86 by flow cytometry. Additionally, L. reuteri stimulated DCs exhibited phenotypic maturation as denoted by cytokine production, including anti-inflammatory IL-10. Using mouse colonic organoids, we found that the microinjection of L. reuteri secreted metabolites and UV-irradiated bacteria was able to promote IL-10 production by DCs, indicating potential epithelial-immune cross-talk. In a TNBS-model of acute colitis, L. reuteri administration significantly improved histological scoring, colonic cytokine mRNA, serum cytokines, and bolstered IL-10 production. CONCLUSIONS: Overall these data demonstrate that both L. reuteri secreted factors and its bacterial components are able to promote DC maturation. This work points to the specific role of L. reuteri in modulating intestinal DCs. NEW & NOTEWORTHY: Lactobacillus reuteri colonizes the mammalian gastrointestinal tract and exerts beneficial effects on host health. However, the mechanisms behind these effects have not been fully explored. In this article, we identified that L. reuteri ATTC PTA 6475 metabolites and surface components promote dendritic cell maturation and IL-10 production. In acute colitis, we also demonstrate that L. reuteri can promote IL-10 and suppress inflammation. These findings may represent a crucial mechanism for maintaining intestinal immune homeostasis.

Children's Eating Behavior Questionnaire Correlated with Body Compositions of Thai Children and Adolescents with Obesity: A Pilot Study.

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, p=0.02) 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), p=0.04]. 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.

Human-Derived Bifidobacterium dentium Modulates the Mammalian Serotonergic System and Gut-Brain Axis.

BACKGROUND & AIMS: The human gut microbiota can regulate production of serotonin (5-hydroxytryptamine [5-HT]) from enterochromaffin cells. However, the mechanisms underlying microbial-induced serotonin signaling are not well understood. METHODS: Adult germ-free mice were treated with sterile media, live Bifidobacterium dentium, heat-killed B dentium, or live Bacteroides ovatus. Mouse and human enteroids were used to assess the effects of B dentium metabolites on 5-HT release from enterochromaffin cells. In vitro and in vivo short-chain fatty acids and 5-HT levels were assessed by mass spectrometry. Expression of tryptophan hydroxylase, short-chain fatty acid receptor free fatty acid receptor 2, 5-HT receptors, and the 5-HT re-uptake transporter (serotonin transporter) were assessed by quantitative polymerase chain reaction and immunostaining. RNA in situ hybridization assessed 5-HT-receptor expression in the brain, and 5-HT-receptor-dependent behavior was evaluated using the marble burying test. RESULTS: B dentium mono-associated mice showed increased fecal acetate. This finding corresponded with increased intestinal 5-HT concentrations and increased expression of 5-HT receptors 2a, 4, and serotonin transporter. These effects were absent in B ovatus-treated mice. Application of acetate and B dentium-secreted products stimulated 5-HT release in mouse and human enteroids. In situ hybridization of brain tissue also showed significantly increased hippocampal expression of 5-HT-receptor 2a in B dentium-treated mice relative to germ-free controls. Functionally, B dentium colonization normalized species-typical repetitive and anxiety-like behaviors previously shown to be linked to 5-HT-receptor 2a. CONCLUSIONS: These data suggest that B dentium, and the bacterial metabolite acetate, are capable of regulating key components of the serotonergic system in multiple host tissues, and are associated with a functional change in adult behavior.

Growth, Body Composition, and Neurodevelopmental Outcomes at 2 Years Among Preterm Infants Fed an Exclusive Human Milk Diet in the Neonatal Intensive Care Unit: A Pilot Study.

Background: Long-term outcomes of preterm infants fed an exclusive human milk-based (EHM) diet using a donor human milk-based fortifier are not well defined. Materials and Methods: Infants ≤1,250 g birth weight (BW) were studied prospectively at two outpatient visits: 12-15 and 18-22 months corrected age (CA). Dual-energy X-ray absorptiometry and Bayley Scales of Infant and Toddler Development III (BSID-III) were performed at 18-22 months CA. Results: In this pilot study, 51 preterm infants (gestational age 27.8 ± 2.6 weeks and BW 893 ± 204 g) were evaluated. While anthropometric z-scores were significantly lower at discharge compared with birth, z-scores returned to birth levels by 12-15 months CA (length and head circumference [HC]) and 18-22 months CA (weight). Body composition at 2 years of age was similar to term-matched controls. Inpatient growth was significantly correlated with bone density, lean mass (LM), and fat-free mass at 18-22 months CA. Increased mother's own milk (MOM) was significantly correlated with decreased fat mass indices. BSID-III showed that 0% of cognitive composite scores were <70. Conclusions: In addition to returning to BW, length, and HC z-scores by 2 years of age, body composition analysis revealed that increase in body size was appropriate as reflected by LM and bone density similar to matched term controls without an increase in fat mass. No child had severe cognitive developmental delay using a cutoff score of 70. Inpatient growth and increased receipt of MOM correlated with favorable growth and body composition outcomes. Positive outcomes as shown in this study to confirm postdischarge safety of an EHM diet during hospitalization.

Premature small for gestational age infants fed an exclusive human milk-based diet achieve catch-up growth without metabolic consequences at 2 years of age.

OBJECTIVE: To compare postdischarge growth, adiposity and metabolic outcomes of appropriate for gestational age (AGA) versus small for gestational age (SGA) premature infants fed an exclusive human milk (HM)-based diet in the neonatal intensive care unit. DESIGN: Premature infants (birth weight ≤1250 g) fed an exclusive HM-based diet were examined at 12-15 months corrected gestational age (CGA) (visit 1) for anthropometrics, serum glucose and non-fasting insulin, and at 18-22 months CGA (visit 2) for body composition by dual-energy X-ray absorptiometry. RESULTS: Of 51 children, 33 were AGA and 18 were SGA at birth. The SGA group had weight gain (g/day) equal to AGA group during the follow-up period. SGA had a significantly greater body mass index (BMI) z-score gain from visit 1 to visit 2 (0.25±1.10 vs -0.21±0.84, p=0.02) reflecting catch-up growth. There were no significant differences in total fat mass (FM) and trunk FM between groups. SGA had significantly lower insulin level (5.0±3.7 vs 17.3±15.1 µU/mL, p=0.02) and homeostatic model of assessment-insulin resistance (1.1±0.9 vs 4.3±4.1, p=0.02). Although regional trunk FM correlated with insulin levels in SGA (r=0.893, p=0.04), they had lower insulin level compared with AGA and no difference in adiposity. CONCLUSIONS: SGA premature infants who received an exclusive HM-based diet exhibited greater catch-up growth without increased adiposity or elevated insulin resistance compared with AGA at 2 years of age. An exclusive HM-based diet may improve long-term body composition and metabolic outcomes of premature infants with ≤1250 g birth weight, specifically SGA.

Low-glycemic index diet may improve insulin sensitivity in obese children.

BACKGROUND: A low-glycemic index (GI) diet may be beneficial for weight management due to its effect on insulin metabolism and satiety. METHODS: Obese children aged 9-16 y were randomly assigned either a low-GI diet or a low-fat diet (control group) for 6 mo. Body composition changes were measured by dual-energy X-ray absorptiometry and bioelectrical impedance analysis. Insulin sensitivity was measured by fasting plasma glucose and insulin. RESULTS: Fifty-two participants completed the study (mean age: 12.0 ± 2.0 y, 35 boys); both groups showed significantly decreased BMI z-score but similar changes in fat and fat-free mass. The low-GI group demonstrated a significant decline in fasting plasma insulin (22.2 ± 14.3 to 13.7 ± 10.9 mU/l; P = 0.004) and homeostatic model of assessment-insulin resistance (4.8 ± 3.3 to 2.9 ± 2.3; P = 0.007), whereas the control group did not. However, general linear model showed no significant difference in insulin resistance between groups after adjusting for baseline levels, suggesting that the greater reduction in insulin resistance in the low-GI group may be explained by higher baseline values. CONCLUSION: Despite subtle effects on body composition, a low-GI diet may improve insulin sensitivity in obese children with high baseline insulin. A bigger study in obese children with insulin resistance could be worthwhile to confirm our findings.

Bleeding tendency in an adolescent with chronic small bowel obstruction.

We report a case of fat-soluble vitamin deficiency in a 14-year old boy who had chronic duodenal obstruction. He presented with periodic unexplained bleeding tendency. The laboratory results showed positive fat globules in stool and prolonged prothrombin time. His further investigation revealed low plasma vitamin A and undetectable plasma vitamin E. After parenteral vitamin K and oral vitamin A and E supplement, these abnormalities resolved although he still had absent knee jerk. We propose that fat malabsorption and fat-soluble vitamin deficiency can occur after prolonged duodenal obstruction that induce bacterial overgrowth following by bile acid deconjugation. Despite very few case reports, screening for fat malabsorption and fat-soluble vitamin deficiency might be warranted in patients with chronic small bowel obstruction.