Digital Intervention for behaviouR changE and Chronic disease prevenTION (DIRECTION): Study protocol for a randomized controlled trial of a web-based platform integrating nutrition, physical activity, and mindfulness for individuals with obesity.

Excess body weight, suboptimal diet, physical inactivity, alcohol consumption, sleep disruption, and elevated stress are modifiable risk factors associated with the development of chronic diseases. Digital behavioural interventions targeting these factors have shown promise in improving health and reducing chronic disease risk. The Digital Intervention for behaviouR changE and Chronic disease prevenTION (DIRECTION) study is a parallel group, two-arm, randomized controlled trial evaluating the effects of adding healthcare professional guidance and peer support via group-based sessions to a web-based wellness platform (experimental group, n = 90) compared to a self-guided use of the platform (active control group, n = 90) among individuals with a body mass index (BMI) of 30 to <35 kg/m2 and aged 40-65 years. Obesity is defined by a high BMI. The web-based wellness platform employed in this study is My Viva Plan (MVP)®, which holistically integrates nutrition, physical activity, and mindfulness programs. Over 16 weeks, the experimental group uses the web-based wellness platform daily and engages in weekly online support group sessions. The active control group exclusively uses the web-based wellness platform daily. Assessments are conducted at baseline and weeks 8 and 16. The primary outcome is between-group difference in weight loss (kg) at week 16, and secondary outcomes are BMI, percent weight change, proportion of participants achieving 5% or more weight loss, dietary intake, physical activity, alcohol consumption, sleep, and stress across the study. A web-based wellness platform may be a scalable approach to promote behavioural changes that positively impact health. This study will inform the development and implementation of interventions using web-based wellness platforms and personalized digital interventions to improve health outcomes and reduce chronic disease risk among individuals with obesity.

Cardiometabolic Health in Adolescents with Obesity: The Role of Protein Intake, Diet Quality, and Physical Activity.

Background: Although adolescents with obesity have an increased risk of cardiometabolic disease, a subset maintains a healthy cardiometabolic profile. Unhealthy lifestyle behaviors may determine cardiometabolic risk. We aimed to characterize the lifestyle behaviors of adolescents with obesity, compare differences between metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUO), and assess associations between lifestyle behaviors and cardiometabolic profiles. Methods: Participants aged 10-18 years with body mass index (BMI) ≥ 95th percentile were included. Dietary intake (DI) was estimated from 3-day food records, and diet quality (DQ) was assessed using the Healthy Eating Index-Canadian Adaptation. Physical activity (PA), body composition, anthropometrics, blood markers, and blood pressure (BP) were objectively measured. MUO was defined as having high triglycerides, BP, glucose, or low high-density lipoprotein. Regression analyses were performed between lifestyle behaviors and cardiometabolic markers. Results: Thirty-nine participants (BMI z-score 2.8 [2.5-3.5], age 12.5 [10.9-13.5] years, 56.4% female) were included. A high proportion of participants failed to meet lifestyle recommendations, particularly for DQ (94.7%, n = 36), fiber (94.7%, n = 36), and PA (90.9%, n = 30). No differences in lifestyle behaviors were found between MUO (59.0%, n = 22) and MHO (41.0%, n = 16). Protein intake was negatively associated with BMI and waist circumference z-scores, fat mass index, insulin resistance, low-density lipoprotein, and C-reactive protein, whereas higher DQ was associated with lower C-reactive protein. Higher light PA levels were associated with lower total cholesterol and triglycerides. Conclusion: Adolescents with either MUO or MHO displayed low adherence to DQ, DI, and PA recommendations; no differences in lifestyle behaviors were found. Protein intake, DQ, and PA were associated with a healthier cardiometabolic profile.

One-Year Changes in Bioelectrical Impedance Data in Adolescent Athletes.

Raw bioelectrical impedance (BI) data and vector analysis (BIVA) have been used to evaluate fat-free mass (FFM) cross-sectionally in adolescent athletes; however, there have been no longitudinal studies about it. This study aimed to assess the magnitude of changes in raw BI data (resistance [R], reactance [Xc], and phase angle [PhA]), BIVA, and FFM in adolescent athletes (n = 137, 40% female). BI data were collected using a single-frequency device at baseline and after one year of sports practice. Baseline chronological age categorized the participants (11, 12, or 13 years [y]). In females, Xc/H increased (13 to 14 y, p = 0.04) while R/H decreased in all age groups (p = 0.001). PhA (11 to 12 y, p = 0.048) and FFM (11 to 12 y and 12 to 13 y groups p = 0.001) increased and showed the lowest magnitude of changes in the 13 to 14 y group (p = 0.05). In males, Xc/H decreased (11 to 12 and 12 to 13 y groups, p = 0.001) with a higher magnitude of changes in the 13 to 14 y group (p = 0.004); R/H decreased (p = 0.001); FFM increased in all groups (p = 0.001); however, no magnitude of changes was observed. PhA increased in the 13 to 14 y group (p = 0.004). BIVA showed no differences among ellipse distances in females. In males, a high distance was observed in the 11 to 12 y group. "Time interval" influenced PhA and Xc/H in the female group and R/H and Xc/H in the male group. "Initial age" and "time interval" influenced the increase in PhA in the male group. Raw BI data and BIVA patterns can detect the magnitude of the changes in a sex-dependent manner.

The metabolic load-capacity model and cardiometabolic health in children and youth with obesity.

BACKGROUND: The metabolic load-capacity index (LCI), which represents the ratio of adipose to skeletal muscle tissue-containing compartments, is potentially associated with cardiometabolic diseases. OBJECTIVES: To examine the associations between the LCI and cardiometabolic risk factors in children and youth with obesity. METHODS: This is a cross-sectional study including 10-18 years-old participants with a BMI of ≥95th . LCI by air-displacement plethysmography (ADP) was calculated as fat mass divided by fat-free mass, and LCI by ultrasound (US) as subcutaneous adipose tissue divided by skeletal muscle thickness. Sex-specific medians stratified participants into high versus low LCI. Single (inflammation, insulin resistance, dyslipidemia and hypertension) and clustered cardiometabolic risk factors were evaluated. Linear and logistic regression models tested the associations between these variables, adjusted for sexual maturation. RESULTS: Thirty-nine participants (43.6% males; 59% mid-late puberty) aged 12.5 (IQR: 11.1-13.5) years were included. LCI by ADP was positively associated with markers of inflammation and dyslipidemia; having a higher LCI predicted dyslipidemia in logistic regression. Similarly, LCI by US was positively associated with markers of dyslipidemia and blood pressure. In mid-late pubertal participants, LCI by US was positively associated with markers of insulin resistance and inflammation. CONCLUSIONS: Participants with unfavourable cardiometabolic profile had higher LCI, suggesting its potential use for predicting and monitoring cardiometabolic health in clinical settings.

Optimizing clinical nutrition research: the role of adaptive and pragmatic trials.

Evidence-based nutritional recommendations address the health impact of suboptimal nutritional status. Efficacy randomized controlled trials (RCTs) have traditionally been the preferred method for determining the effects of nutritional interventions on health outcomes. Nevertheless, obtaining a holistic understanding of intervention efficacy and effectiveness in real-world settings is stymied by inherent constraints of efficacy RCTs. These limitations are further compounded by the complexity of nutritional interventions and the intricacies of the clinical context. Herein, we explore the advantages and limitations of alternative study designs (e.g., adaptive and pragmatic trials), which can be incorporated into RCTs to optimize the efficacy or effectiveness of interventions in clinical nutrition research. Efficacy RCTs often lack external validity due to their fixed design and restrictive eligibility criteria, leading to efficacy-effectiveness and evidence-practice gaps. Adaptive trials improve the evaluation of nutritional intervention efficacy through planned study modifications, such as recalculating sample sizes or discontinuing a study arm. Pragmatic trials are embedded within clinical practice or conducted in settings that resemble standard of care, enabling a more comprehensive assessment of intervention effectiveness. Pragmatic trials often rely on patient-oriented primary outcomes, acquire outcome data from electronic health records, and employ broader eligibility criteria. Consequently, adaptive and pragmatic trials facilitate the prompt implementation of evidence-based nutritional recommendations into clinical practice. Recognizing the limitations of efficacy RCTs and the potential advantages of alternative trial designs is essential for bridging efficacy-effectiveness and evidence-practice gaps. Ultimately, this awareness will lead to a greater number of patients benefiting from evidence-based nutritional recommendations.

Evaluation of Autonomic Nervous System Dysfunction in Childhood Obesity and Prader-Willi Syndrome.

The autonomic nervous system (ANS) may play a role in the distribution of body fat and the development of obesity and its complications. Features of individuals with Prader-Willi syndrome (PWS) impacted by PWS molecular genetic classes suggest alterations in ANS function; however, these have been rarely studied and presented with conflicting results. The aim of this study was to investigate if the ANS function is altered in PWS. In this case-control study, we assessed ANS function in 20 subjects with PWS (6 males/14 females; median age 10.5 years) and 27 body mass index (BMI) z-score-matched controls (19 males/8 females; median age 12.8 years). Standardized non-invasive measures of cardiac baroreflex function, heart rate, blood pressure, heart rate variability, quantitative sudomotor axon reflex tests, and a symptom questionnaire were completed. The increase in heart rate in response to head-up tilt testing was blunted (p < 0.01) in PWS compared to controls. Besides a lower heart rate ratio with Valsalva in PWS (p < 0.01), no significant differences were observed in other measures of cardiac function or sweat production. Findings suggest possible altered sympathetic function in PWS.

Prevalence and clinical implications of abnormal body composition phenotypes in patients with COVID-19: a systematic review.

BACKGROUND: The impact of body composition (BC) abnormalities on COVID-19 outcomes remains to be determined. OBJECTIVES: We summarized the evidence on BC abnormalities and their relationship with adverse clinical outcomes in patients with COVID-19. METHODS: A systematic search was conducted up until 26 September, 2022 for observational studies using BC techniques to quantify skeletal muscle mass (or related compartments), muscle radiodensity or echo intensity, adipose tissue (AT; or related compartments), and phase angle (PhA) in adults with COVID-19. Methodological quality of studies was assessed using the Newcastle-Ottawa Scale. A synthesis without meta-analysis was conducted to summarize the prevalence of BC abnormalities and their significant associations with clinical outcomes. RESULTS: We included 62 studies (69.4% low risk of bias) with 12-1138 participants, except 3 studies with ≤490,301 participants. Using CT and different cutoff values, prevalence ranged approximately from 22% to 90% for low muscle mass, 12% to 85% for low muscle radiodensity, and 16% to 70% for high visceral AT. Using BIA, prevalence of high FM was 51%, and low PhA was 22% to 88%. Mortality was inversely related to PhA (3/4 studies) and positively related to intra- and intermuscular AT (4/5 studies), muscle echo intensity (2/2 studies), and BIA-estimated FM (2/2 studies). Intensive care unit (ICU) admission was positively related to visceral AT (6/7 studies) and total AT (2/3 studies). Disease severity and hospitalization outcomes were positively related to intra- and intermuscular AT (2/2 studies). Inconsistent associations were found for the rest of the BC measures and hospitalization outcomes. CONCLUSIONS: Abnormalities in BC were prevalent in patients with COVID-19. Although conflicting associations were observed among certain BC abnormalities and clinical outcomes, higher muscle echo intensity (reflective of myosteatosis) and lower PhA were more consistently associated with greater mortality risk. Likewise, high intra- and intermuscular AT and visceral AT were associated with mortality and ICU admission, respectively. This trial was registered at PROSPERO as CRD42021283031.

Phase angle and cellular health: inflammation and oxidative damage.

Phase angle is a composite measure that combines two raw bioelectrical impedance analysis measures: resistance and reactance. Phase angle has been considered an indicator of cellular health, integrity, and hydration. As inflammation and oxidative stress can damage cellular structures, phase angle has potential utility in early detecting inflammatory and oxidative status. Herein, we aimed to critically review the current understanding on the determinants of phase angle and its relationship with markers of inflammation and oxidative stress. We also discussed the potential role of phase angle in detecting chronic inflammation and related adverse outcomes. Several factors have been identified as predictors of phase angle, including age, sex, extracellular to intracellular water ratio, and fat-free mass. In addition to these factors, body mass index (BMI) also seems to influence phase angle. Available data also show that lower phase angle values are correlated (negligible to high correlation coefficients) with higher c-reactive protein, tumour necrosis factor-α, interleukin-6, and interleukin-10 in studies involving the general and aging populations, as well as patients with chronic conditions. Although fewer studies have evaluated the relationship between phase angle and markers of oxidative stress, available data also suggest that phase angle has potential to be used as an indicator (for screening) of oxidative damage. Future studies including diverse populations and bioelectrical impedance devices are required to confirm the validity and accuracy of phase angle as a marker of inflammation and oxidative stress for clinical use.

Computed tomography-based body composition measures in COPD and their association with clinical outcomes: A systematic review.

BACKGROUND: Computed tomography (CT) is commonly utilized in chronic obstructive pulmonary disease (COPD) for lung cancer screening and emphysema characterization. Computed tomography-morphometric analysis of body composition (muscle mass and adiposity) has gained increased recognition as a marker of disease severity and prognosis. This systematic review aimed to describe the CT-methodology used to assess body composition and identify the association of body composition measures and disease severity, health-related quality of life (HRQL), cardiometabolic risk factors, respiratory exacerbations, and survival in patients with COPD. METHODS: Six databases were searched (inception-September 2021) for studies evaluating adult COPD patients using thoracic or abdominal CT-muscle or adiposity body composition measures. The systematic review was conducted in accordance with the PRISMA guidelines. RESULTS: Twenty eight articles were included with 15,431 COPD patients, across all GOLD stages with 77% males, age range (mean/median 59-78 years), and BMI range 19.8-29.3 kg/m2. There was heterogeneity in assessment of muscle mass and adiposity using thoracic (n = 22) and abdominal (n = 8) CT-scans, capturing different muscle groups, anatomic locations, and adiposity compartments (visceral, subcutaneous, and epicardial). Low muscle mass and increased adiposity were associated with increased COPD severity measures (lung function, exercise capacity, dyspnea) and lower HRQL, but were not consistent across studies. Increased visceral adiposity (n = 6) was associated with cardiovascular disease or risk factors (hypertension, hyperlipidemia, and diabetes). Low muscle CSA was prognostic of respiratory exacerbations or mortality in three of six studies, whereas the relationship with increased intermuscular adiposity and greater mortality was only observed in one of three studies. CONCLUSION: There was significant variability in CT-body composition measures. In several studies, low muscle mass was associated with increased disease severity and lower HRQL, whereas adiposity with cardiovascular disease/risk factors. Given the heterogeneity in body composition measures and clinical outcomes, the prognostic utility of CT-body composition in COPD requires further study.

Dietary choices after a cancer diagnosis: A narrative review.

Individuals with cancer may be motivated to make lifestyle changes and informed dietary choices, but are exposed to conflicting and erroneous nutrition information, particularly from online and social media sources. Changes to dietary choices that stem from a diagnosis of cancer are not fully understood. Thus, we conducted a narrative review to summarize the literature focused on dietary choices after a cancer diagnosis, and highlighted influential factors. Postdiagnosis dietary changes have been studied primarily in female patients with breast cancer in European countries. Reported changes typically included decreased red and processed meat intake and increased consumption of fruits and vegetables. These changes align with the recommendations for cancer prevention but were implemented after diagnosis, and may not meet nutrition guidelines for patients with cancer. Age and time since diagnosis were among the influential factors that affected these postdiagnosis changes. Data on dietary changes implemented after a diagnosis of varying cancer types in the North American population are lacking, and would provide practitioners with an enhanced understanding of patient information needs and reasons for dietary choices.

The Impact of Long COVID-19 on Muscle Health.

COVID-19 negatively impacts several organs and systems weeks or months after initial diagnosis. Skeletal muscle can be affected, leading to fatigue, lower mobility, weakness, and poor physical performance. Older adults are at increased risk of developing musculoskeletal symptoms during long COVID. Systemic inflammation, physical inactivity, and poor nutritional status are some of the mechanisms leading to muscle dysfunction in individuals with long COVID. Current evidence suggests that long COVID negatively impacts body composition, muscle function, and quality of life. Muscle mass and function assessments can contribute toward the identification, diagnosis, and management of poor muscle health resulting from long COVID.

Recent Advances in Incretin-Based Pharmacotherapies for the Treatment of Obesity and Diabetes.

The incretin hormone glucagon-like peptide-1 (GLP-1) has received enormous attention during the past three decades as a therapeutic target for the treatment of obesity and type 2 diabetes. Continuous improvement of the pharmacokinetic profile of GLP-1R agonists, starting from native hormone with a half-life of ~2-3 min to the development of twice daily, daily and even once-weekly drugs highlight the pharmaceutical evolution of GLP-1-based medicines. In contrast to GLP-1, the incretin hormone glucose-dependent insulinotropic polypeptide (GIP) received little attention as a pharmacological target, because of conflicting observations that argue activation or inhibition of the GIP receptor (GIPR) provides beneficial effects on systemic metabolism. Interest in GIPR agonism for the treatment of obesity and diabetes was recently propelled by the clinical success of unimolecular dual-agonists targeting the receptors for GIP and GLP-1, with reported significantly improved body weight and glucose control in patients with obesity and type II diabetes. Here we review the biology and pharmacology of GLP-1 and GIP and discuss recent advances in incretin-based pharmacotherapies.

Mapping ongoing nutrition intervention trials in muscle, sarcopenia, and cachexia: a scoping review of future research.

Muscle loss alone, or in the context of sarcopenia or cachexia, is a prevalent condition and a predictor of negative outcomes in aging and disease. As adequate nutrition is essential for muscle maintenance, a growing number of studies has been conducted to explore the role of specific nutrients on muscle mass or function. Nonetheless, more research is needed to guide evidence-based recommendations. This scoping review aimed to compile and document ongoing clinical trials investigating nutrition interventions as a strategy to prevent or treat low muscle mass or function (strength and physical performance), sarcopenia, or cachexia. ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform were searched up to 21 April 2021 for planned and ongoing trials. Randomized controlled trials with ≥20 participants per arm were included based on intent to explore the effects of nutrition interventions on muscle-related outcomes (i.e. muscle mass or strength, physical performance, or muscle synthesis rate) in both clinical and non-clinical conditions (i.e. aging). Two reviewers independently screened records for eligibility, and a descriptive synthesis of trials characteristics was conducted. A total of 113 trials were included in the review. Most trials (69.0%) enroll adults with clinical conditions, such as cancer (19.5%), obesity and metabolic diseases (16.8%), and musculoskeletal diseases (10.7%). The effects of nutrition interventions on age-related muscle loss are explored in 31% of trials. Although nutrition interventions of varied types were identified, food supplements alone (48.7%) or combined with dietary advice (11.5%) are most frequently reported. Protein (17.7%), amino acids (10.6%), and ß-hydroxy-ß-methylbutyrate (HMB, 6.2%) are the top three food supplements' nutrients under investigation. Primary outcome of most trials (54.9%) consists of measures of muscle mass alone or in combination with muscle strength and/or performance (as either primary or secondary outcomes). Muscle strength and physical performance are primary outcomes of 38% and 31.9% of the trials, respectively. These measurements were obtained using a variety of techniques. Only a few trials evaluate muscle synthesis rate either as a primary or secondary outcome (5.3%). Several nutrition studies focusing on muscle, sarcopenia, and cachexia are underway and can inform future research in this area. Although many trials have similar type of interventions, methodological heterogeneity may challenge study comparisons, and future meta-analyses aiming to provide evidence-based recommendations. Upcoming research in this area may benefit from guidelines for the assessment of therapeutic effects of nutrition interventions.

Effects of ß-hydroxy ß-methylbutyrate (HMB) supplementation on muscle mass, function, and other outcomes in patients with cancer: a systematic review.

Low muscle mass is prevalent among patients with cancer and a predictor of adverse clinical outcomes. To counteract muscle loss, ß-hydroxy ß-methylbutyrate (HMB) supplementation has been proposed as a potential therapy for older adults and various diseases states. This systematic review aimed to investigate the effects and safety of HMB supplementation in relation to muscle mass and function and other clinical outcomes in patients with cancer. A systematic search of MEDLINE, CINAHL, Embase, Cochrane Central Register of Controlled Trials, Scopus, ProQuest, and grey literature for reports published from inception to December 2021 was conducted. Included studies provided supplements containing any dose of HMB to adult patients with active cancer. A synthesis without meta-analysis was conducted using a vote-counting approach based solely on the direction of the effect (i.e. regardless of statistical significance). Risk of bias was assessed for each outcome domain, and evidence from higher-quality studies (i.e. those with either low or moderate risk of bias) was examined. Safety was evaluated using both lower-quality and higher-quality studies. Fifteen studies were included, in which six were randomized controlled trials in patients with various cancer types and treatments. Studies prescribed HMB combined with amino acids (73.3%), HMB in oral nutritional supplements (20.0%), or both supplement types (6.7%); Ca-HMB doses of 3.0 g/day were provided in 80.0% of the studies. Four studies had high risk of bias across all outcome domains. Considering the higher-quality studies, evidence of a beneficial effect of HMB supplementation was found in four of four studies for muscle mass, two of two for muscle function, three of three for hospitalization, and five of seven for survival. In contrast, no beneficial effects of HMB on quality of life or body weight was found in two of four and three of five studies, respectively. A limited number of higher-quality studies evaluating the impact of HMB on cancer therapy-related toxicity, inflammation, and tumour response were observed. No serious adverse effects directly related to the nutrition intervention were reported. Although limited, current evidence suggests that HMB supplementation has a beneficial effect on muscle mass and function in patients with cancer. Well-designed trials are needed to further explore the clinical benefit of HMB supplementation in this patient population.

Using bioelectrical impedance analysis in children and adolescents: Pressing issues.

Single- and multifrequency bioelectrical impedance analysis (BIA) has gained popularity as a tool to assess body composition and health status of children and adolescents, but many questions and misconceptions remain. This review addresses pressing issues researchers and health care providers may encounter when using BIA in the young population. The importance of choosing population-specific and device-specific equations to estimate body composition as well as the use of BIA in longitudinal analyses are discussed. When specific equations are not available, raw bioimpedance values (i.e., resistance, reactance, and impedance) can be used to compute bioimpedance parameters, such as phase angle, impedance ratio, and bioelectrical impedance vector analysis. As interpreting these parameters is challenging, suggestions are provided on the use of reference data, cut-off points, and adjustment factors. Furthermore, unsolved technical and analytical issues are listed. Based on existing issues and potential for future development, a greater interaction between industry and academic researchers to improve the validity of BIA measurements among children and adolescents across their developmental stages is encouraged.

Composition and Functions of the Gut Microbiome in Pediatric Obesity: Relationships with Markers of Insulin Resistance.

The gut microbiome is hypothesized to play a crucial role in the development of obesity and insulin resistance (IR); the pathways linking the microbiome to IR in pediatrics have yet to be precisely characterized. We aimed to determine the relationship between the gut microbiome composition and metabolic functions and IR in children with obesity. In a cross-sectional study, fecal samples from children with obesity (10-16 years old) were collected for taxonomical and functional analysis of the fecal microbiome using shotgun metagenomics. The homeostatic model assessment for insulin resistance (HOMA-IR) was determined using fasting glucose and insulin. Associations between HOMA-IR and α-diversity measures as well as metabolic pathways were evaluated using Spearman correlations; relationships between HOMA-IR and ß-diversity were assessed by permutational multivariate analysis of variance. Twenty-one children (nine males; median: age = 12.0 years; BMI z-score = 2.9; HOMA-IR = 3.6) completed the study. HOMA-IR was significantly associated with measures of α-diversity but not with ß-diversity. Children with higher HOMA-IR exhibited lower overall species richness, Firmicutes species richness, and overall Proteobacteria species Shannon diversity. Furthermore, HOMA-IR was inversely correlated with the abundance of pathways related to the biosynthesis of lipopolysaccharides, amino acids, and short-chain fatty acids, whereas positive correlations between HOMA-IR and the peptidoglycan biosynthesis pathways were observed. In conclusion, insulin resistance was associated with decreased microbial α-diversity measures and abundance of genes related to the metabolic pathways. Our study provides a framework for understanding the microbial alterations in pediatric obesity.

Probiotics, prebiotics, synbiotics, and fecal microbiota transplantation in the treatment of behavioral symptoms of autism spectrum disorder: A systematic review.

The emerging role of a microbiota-gut-brain axis in autism spectrum disorder (ASD) suggests that modulating gut microbial composition may offer a tractable approach to addressing the lifelong challenges of ASD. The aim of this systematic review was to provide an overview and critically evaluate the current evidence on the efficacy and safety of probiotic, prebiotic, synbiotic, and fecal microbiota transplantation therapies for core and co-occurring behavioral symptoms in individuals with ASD. Comprehensive searches of MEDLINE, EMBASE, Scopus, Web of Science Core Collection, Cochrane Library, and Google Scholar were performed from inception to March 5, 2020, and two update searches were completed on October 25, 2020, and April 22, 2021, respectively. A total of 4306 publications were identified, of which 14 articles met the inclusion criteria. Data were extracted independently by two reviewers using a preconstructed form. Results of probiotic studies do not confirm the supposed beneficial effect of probiotics on ASD, whereas prebiotics and synbiotic combinations appear to be efficacious in selective behavioral symptoms. Evidence of the efficacy of fecal microbiota transplantation in ASD is still scarce but supports further research. Overall, the current evidence base to suggest beneficial effects of these modalities in ASD is limited and inconclusive. More clinical trials are currently looking at the use of microbial-based therapies in ASD. With a robust double-blind randomized controlled protocol to investigate the efficacy, these trials should provide significant and definitive results. LAY SUMMARY: There is a link between altered gut bacteria and autism spectrum disorder. Some people believe that modulating bacterial composition in the gut may help reduce autism symptoms, but evidence from human studies suggesting beneficial effects of probiotic, prebiotic, and combination thereof as well as fecal transplants in autism spectrum disorder is limited and inconclusive. Current data should not encourage use of these modalities. Further clinical studies are needed.

Efficacy of metformin and fermentable fiber combination therapy in adolescents with severe obesity and insulin resistance: study protocol for a double-blind randomized controlled trial.

BACKGROUND: Accumulating evidence suggests that the metabolic effects of metformin and fermentable fibers are mediated, in part, through diverging or overlapping effects on the composition and metabolic functions of the gut microbiome. Pre-clinical animal models have established that the addition of fiber to metformin monotherapy improves glucose tolerance. However, possible synergistic effects of combination therapy (metformin plus fiber) have not been investigated in humans. Moreover, the underlying mechanisms of synergy have yet to be elucidated. The aim of this study is to compare in adolescents with obesity the metabolic effects of metformin and fermentable fibers in combination with those of metformin or fiber alone. We will also determine if therapeutic responses correlate with compositional and functional features of the gut microbiome. METHODS: This is a parallel three-armed, double-blinded, randomized controlled trial. Adolescents (aged 12-18 years) with obesity, insulin resistance (IR), and a family history of type 2 diabetes mellitus (T2DM) will receive either metformin (850 mg p.o. twice/day), fermentable fibers (35 g/day), or a combination of metformin plus fiber for 12 months. Participants will be seen at baseline, 3, 6, and 12 months, with a phone follow-up at 1 and 9 months. Primary and secondary outcomes will be assessed at baseline, 6, and 12 months. The primary outcome is change in IR estimated by homeostatic model assessment of IR; key secondary outcomes include changes in the Matsuda index, oral disposition index, body mass index z-score, and fat mass to fat-free mass ratio. To gain mechanistic insight, endpoints that reflect host-microbiota interactions will also be assessed: obesity-related immune, metabolic, and satiety markers; humoral metabolites; and fecal microbiota composition, short-chain fatty acids, and bile acids. DISCUSSION: This study will compare the potential metabolic benefits of fiber with those of metformin in adolescents with obesity, determine if metformin and fiber act synergistically to improve IR, and elucidate whether the metabolic benefits of metformin and fiber associate with changes in fecal microbiota composition and the output of health-related metabolites. This study will provide insight into the potential role of the gut microbiome as a target for enhancing the therapeutic efficacy of emerging treatments for T2DM prevention. TRIAL REGISTRATION: ClinicalTrials.gov NCT04578652 . Registered on 8 October 2020.

Validity and accuracy of body fat prediction equations using anthropometrics measurements in adolescents.

BACKGROUND: The pediatric relative fat mass (RFM) has been recently presented and validated as an index for estimating percentage body fat (%BF) in North American children and adolescents. Similar to body mass index (BMI) and tri-ponderal mass index (TMI), RFM uses anthropometric measures (i.e., weight, height and waist circumference) to estimate body composition. The primary purpose of this study was to validate the newly developed RFM equation for %BF prediction in Southern Brazilian adolescents; as secondary objective, we compared %BF estimation from BMI- and TMI-derived equations. METHODS: A total of 631 individuals (434 boys) aged 11 to 18 were analyzed. Bland-Altman analyses were used to determine concordance between predicted equations and %BF measured by DXA; results are presented using mean difference (i.e., bias) and standard deviation. Sensitivity and specificity were calculated for %BF percentile classifications. RESULTS: RFM underestimated %BF in 65.2% of boys (- 4.3 ± 2.8%) and 84.8% of girls (- 5.3 ± 2.7%). In contrast, TMI overestimated %BF in 62.9% of boys (4.0 ± 2.9%) and 56.3% (3.5 ± 3.0%) of girls. The performance of BMI showed mixed results; %BF was overestimated in 68.4% of boys (5.0 ± 4.0%) and underestimated in 67.5% of girls (- 3.9 ± 2.6%), all p < 0.001. Although, RFM had the highest specificity for %BF percentile classifications, sensitivity was low and inferior to BMI and TMI. CONCLUSION: TMI was superior to RFM and BMI in predicting %BF in Southern Brazilian adolescents. Using RFM, BMI or TMI equations for %BF prediction without a population-specific correction factor may lead to incorrect interpretations. We suggest that correction factors should be investigated to improve the accuracy of these surrogate indices for body composition assessment. LEVEL OF EVIDENCE: Level V, cross sectional descriptive study.

Myokines in treatment-naïve patients with cancer-associated cachexia.

Cancer-associated cachexia is a complex metabolic syndrome characterized by weight loss and systemic inflammation. Muscle loss and fatty infiltration into muscle are associated with poor prognosis in cancer patients. Skeletal muscle secretes myokines, factors with autocrine, paracrine and/or endocrine action, which may be modified by or play a role in cachexia. This study examined myokine content in the plasma, skeletal muscle and tumor homogenates from treatment-naïve patients with gastric or colorectal stages I-IV cancer with cachexia (CC, N = 62), or not (weight stable cancer, WSC, N = 32). Myostatin, interleukin (IL) 15, follistatin-like protein 1 (FSTL-1), fatty acid binding protein 3 (FABP3), irisin and brain-derived neurotrophic factor (BDNF) protein content in samples was measured with Multiplex technology; body composition and muscle lipid infiltration were evaluated in computed tomography, and quantification of triacylglycerol (TAG) in the skeletal muscle. Cachectic patients presented lower muscle FSTL-1 expression (p = 0.047), higher FABP3 plasma content (p = 0.0301) and higher tumor tissue expression of FABP3 (p = 0.0182), IL-15 (p = 0.007) and irisin (p = 0.0110), compared to WSC. Neither muscle TAG content, nor muscle attenuation were different between weight stable and cachectic patients. Lumbar adipose tissue (AT) index, visceral AT index and subcutaneous AT index were lower in CC (p = 0.0149, p = 0.0455 and p = 0.0087, respectively), who also presented lower muscularity in the cohort (69.2% of patients; p = 0.0301), compared to WSC. The results indicate the myokine profile in skeletal muscle, plasma and tumor is impacted by cachexia. These findings show that myokines eventually affecting muscle wasting may not solely derive from the muscle itself (as the tumor also may contribute to the systemic scenario), and put forward new perspectives on cachexia treatment targeting myokines and associated receptors and pathways.