https://www.commed.vcu.edu/Chronic_Disease/2012/cochranrvwrschbias.pdf

The Cochrane Collaboration's tool for assessing risk of bias in randomised trials

https://escholarship.org/content/qt7mq4n8xg/qt7mq4n8xg.pdf?t=pwouye

The Central Nervous System and the Gut Microbiome

Autism spectrum disorders (ASD) are complex neurobiological disorders that impair social interactions and communication and lead to restricted, repetitive, and stereotyped patterns of behavior, interests, and activities. The causes of these disorders remain poorly understood, but gut microbiota, the 1013 bacteria in the human intestines, have been implicated because children with ASD often suffer gastrointestinal (GI) problems that correlate with ASD severity. Several previous studies have reported abnormal gut bacteria in children with ASD. The gut microbiome-ASD connection has been tested in a mouse model of ASD, where the microbiome was mechanistically linked to abnormal metabolites and behavior. Similarly, a study of children with ASD found that oral non-absorbable antibiotic treatment improved GI and ASD symptoms, albeit temporarily. Here, a small open-label clinical trial evaluated the impact of Microbiota Transfer Therapy (MTT) on gut microbiota composition and GI and ASD symptoms of 18 ASD-diagnosed children. MTT involved a 2-week antibiotic treatment, a bowel cleanse, and then an extended fecal microbiota transplant (FMT) using a high initial dose followed by daily and lower maintenance doses for 7–8 weeks. The Gastrointestinal Symptom Rating Scale revealed an approximately 80% reduction of GI symptoms at the end of treatment, including significant improvements in symptoms of constipation, diarrhea, indigestion, and abdominal pain. Improvements persisted 8 weeks after treatment. Similarly, clinical assessments showed that behavioral ASD symptoms improved significantly and remained improved 8 weeks after treatment ended. Bacterial and phagedeep sequencing analyses revealed successful partial engraftment of donor microbiota and beneficial changes in the gut environment. Specifically, overall bacterial diversity and the abundance of Bifidobacterium, Prevotella, and Desulfovibrio among other taxa increased following MTT, and these changes persisted after treatment stopped (followed for 8 weeks). This exploratory, extended-duration treatment protocol thus appears to be a promising approach to alter the gut microbiome and virome and improve GI and behavioral symptoms of ASD. Improvements in GI symptoms, ASD symptoms, and the microbiome all persisted for at least 8 weeks after treatment ended, suggesting a long-term impact. This trial was registered on the ClinicalTrials.gov, with the registration number 
 NCT02504554

/pdf/microbiota-transfer-therapy-alters-gut-ecosystem-and-56tl9m3jqc.pdf

Microbiota Transfer Therapy alters gut ecosystem and improves gastrointestinal and autism symptoms: an open-label study

https://www.cell.com/trends/molecular-medicine/pdf/S1471-4914(14)00081-1.pdf

Microbiota and neurodevelopmental windows: implications for brain disorders

https://www.cell.com/cell-host-microbe/pdf/S1931-3128(15)00169-9.pdf

Control of Brain Development, Function, and Behavior by the Microbiome

BACKGROUND: In pediatric settings, parents often raise concerns about possible gastrointestinal (GI) symptoms in autism spectrum disorder (ASD), yet the specificity of these concerns are not well studied. OBJECTIVE: To conduct a meta-analysis of research investigating GI symptoms among children with ASD. METHODS: We searched Medline, PsycINFO, and PubMed databases (1980–2012) in peer-reviewed journals. Analysis involved studies with a comparison group presenting quantitative data on GI symptoms using combinations of terms for ASD and GI indicators. The systematic search yielded 15 studies. We calculated effect sizes and 95% confidence intervals (CIs) using a random-effects model. RESULTS: Children with ASD experience significantly more general GI symptoms than comparison groups, with a standardized mean difference of 0.82 (0.24) and a corresponding odds ratio (OR) of 4.42 (95% CI, 1.90–10.28). Analysis also indicated higher rates of diarrhea (OR, 3.63; 95% CI, 1.82–7.23), constipation (OR, 3.86; 95% CI, 2.23–6.71), and abdominal pain (OR, 2.45; 95% CI, 1.19–5.07). CONCLUSIONS: Results indicate greater prevalence of GI symptoms among children with ASD compared with control children. Identified studies involved high methodological variability and lack of comprehensive data prohibited analysis of GI pathophysiologies (eg, gastroesophageal reflux) typically associated with organic etiologies, limiting conclusions about the underpinnings of the observed association. Future research must address critical questions about the causes and long-term impact of GI symptoms in ASD. Such analyses will require more systematic research and clinical activities, including improved diagnostic screening, standardized assessment, and exploration of potential moderators (eg, dietary restrictions).

Gastrointestinal Symptoms in Autism Spectrum Disorder: A Meta-analysis

We conducted a comprehensive review and meta-analysis of research regarding feeding problems and nutrient status among children with autism spectrum disorders (ASD) The systematic search yielded 17 prospective studies involving a comparison group Using rigorous meta-analysis techniques, we calculated the standardized mean difference (SMD) with standard error and corresponding odds ratio (OR) with 95 % confidence intervals (CI) Results indicated children with ASD experienced significantly more feeding problems versus peers, with an overall SMD of 089 (008) and a corresponding OR of 511, 95 % CI 374–697 Nutrient analyses indicated significantly lower intake of calcium (SMD: −065 [029]; OR: 031, 95 % CI 011–085) and protein (SMD: −058 [025]; OR: 035, 95 % CI: 014–056) in ASD Future research must address critical questions regarding the cause, long-term impact, and remediation of atypical feeding in this population

Feeding Problems and Nutrient Intake in Children with Autism Spectrum Disorders: A Meta-analysis and Comprehensive Review of the Literature

The human gut harbors a complex community of microbes that profoundly influence many aspects of growth and development, including development of the nervous system. Advances in high-throughput DNA sequencing methods have led to rapidly expanding knowledge about this gut microbiome. Here, we review fundamental emerging data on the human gut microbiome, with a focus on potential interactions between the microbiome and autism spectrum disorders (ASD) and consider research on atypical patterns of feeding and nutrition in ASD and how they might interact with the microbiome. Finally we selectively survey results from studies in rodents on the impact of the microbiome on neurobehavioral development. The evidence reviewed here suggests that a deeper understanding of the gut microbiome could open up new avenues of research on ASD, including potential novel treatment strategies.

/pdf/the-gut-microbiome-a-new-frontier-in-autism-research-2ujjyfyjb6.pdf

The Gut Microbiome: A New Frontier in Autism Research

A systematic review of the literature regarding treatment of pediatric feeding disorders was conducted. Articles in peer-reviewed scientific journals (1970-2010) evaluating treatment of severe food refusal or selectivity were identified. Studies demonstrating strict experimental control were selected and analyzed. Forty-eight single-case research studies reporting outcomes for 96 participants were included in the review. Most children presented with complex medical and developmental concerns and were treated at multidisciplinary feeding disorders programs. All studies involved behavioral intervention; no well-controlled studies evaluating feeding interventions by other theoretical perspectives or clinical disciplines met inclusion criteria. Results indicated that behavioral intervention was associated with significant improvements in feeding behavior. Clinical and research implications are discussed, including movement toward the identification of key behavioral antecedents and consequences that promote appropriate mealtime performance, as well as the need to better document outcomes beyond behavioral improvements, such as changes in anthropometric parameters, generalization of treatment gains to caregivers, and improvements in nutritional status.

Pediatric Feeding Disorders: A Quantitative Synthesis of Treatment Outcomes

A Systematic Review and Meta-Analysis of Intensive Multidisciplinary Intervention for Pediatric Feeding Disorders: How Standard Is the Standard of Care?

William G. Sharp

Papers

Gastrointestinal Symptoms in Autism Spectrum Disorder: A Meta-analysis

Feeding Problems and Nutrient Intake in Children with Autism Spectrum Disorders: A Meta-analysis and Comprehensive Review of the Literature

The Gut Microbiome: A New Frontier in Autism Research

Pediatric Feeding Disorders: A Quantitative Synthesis of Treatment Outcomes

A Systematic Review and Meta-Analysis of Intensive Multidisciplinary Intervention for Pediatric Feeding Disorders: How Standard Is the Standard of Care?