Effect of Milk Oligosaccharides and Bifidobacteria on the Intestinal Microflora of Children With Autism

Not Applicable

Completed

Conditions: Autism

Interventions: Dietary Supplement: Synbiotic
Dietary Supplement: Prebiotic

Registration Number: NCT02086110

Lead Sponsor: University of California, Davis

Brief Summary: The purpose of this study is to determine the tolerability of dietary supplements and if these supplements can promote a healthy bacterial environment in the intestines of children with autism spectrum disorders and gastrointestinal complaints.

Detailed Description: This study investigates the feasibility, tolerability, and effects of a dietary supplement on the intestinal flora of children with autism spectrum disorders. This study is divided into two parts, each five weeks long, with a two week break in between. During one part of the study, a prebiotic (milk oligosaccharides from bovine colostrum) will be given. During the other part of the study, the synbiotic composed of the prebiotic and probiotic (bifidobacterium infantis) will be given. Stool will be analyzed at the end of each study arm to determine content of bifidobacteria.

On May 8, 2018, we updated the study start and completion dates to the actual (instead of anticipated) dates.

On May 30-31, 2019, we updated the study results section.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 11

Inclusion Criteria

Autism
Diarrhea and/or constipation

Exclusion Criteria

Milk protein or other documented food allergy
Lactose intolerance
Compromised Immunity
GI conditions (inflammatory bowel disease, celiac disease, short gut, etc.)
Systemic steroid, antifungal, or antibiotic use within a month of starting the study
Failure to thrive
Medically prescribed diets or supplements (including probiotic use within the past month).
Vegetarian or dairy restricted diet
Other medical conditions (seizures, genetic disorders, liver/pancreatic disease, cystic fibrosis, etc.)
Medications that interfere or alter intestinal motility or microbiota composition.
Full scale intelligence quotient (IQ) <40

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Prebiotic only first, then synbiotic	Prebiotic	This group will receive prebiotic only (bovine milk oligosaccharides, administered orally twice per day for a daily total of 0.3 g per pound of body weight) for the first five weeks, followed by a two week break with no treatment, and then will receive the synbiotic (Bifidobacterium infantis (10 billion CFU) twice a day plus 0.3 g per pound body weight of bovine milk oligosaccharides in two divided doses per day orally) for the next five weeks.
Synbiotic first, then prebiotic only	Synbiotic	This group will receive the synbiotic (Bifidobacterium infantis (10 billion CFU) twice a day plus 0.3 g per pound body weight of bovine milk oligosaccharides in two divided doses per day orally) for the first five weeks, followed by a two week break with no treatment, and then will receive the prebiotic only (bovine milk oligosacharrides, administered orally twice per day for a daily total of 0.3 g per pound of body weight) for the next five weeks.
Synbiotic first, then prebiotic only	Prebiotic	This group will receive the synbiotic (Bifidobacterium infantis (10 billion CFU) twice a day plus 0.3 g per pound body weight of bovine milk oligosaccharides in two divided doses per day orally) for the first five weeks, followed by a two week break with no treatment, and then will receive the prebiotic only (bovine milk oligosacharrides, administered orally twice per day for a daily total of 0.3 g per pound of body weight) for the next five weeks.
Prebiotic only first, then synbiotic	Synbiotic	This group will receive prebiotic only (bovine milk oligosaccharides, administered orally twice per day for a daily total of 0.3 g per pound of body weight) for the first five weeks, followed by a two week break with no treatment, and then will receive the synbiotic (Bifidobacterium infantis (10 billion CFU) twice a day plus 0.3 g per pound body weight of bovine milk oligosaccharides in two divided doses per day orally) for the next five weeks.

Primary Outcome Measures

Name	Time	Method
Stool Microbiota Composition Change During Prebiotic Only Treatment	Five weeks	The stool microbiome composition will be analyzed through next generation sequencing and quantitative polymerase chain reaction. Overall bacterial composition change is reported here, as change in enterotype from before prebiotic only treatment to after prebiotic treatment, for all subjects. Enterotypes were organized into four categories for analysis: a community high in Prevotella ("Prevotella"), a community high in Bifidobacterium ("Bifidobacterium"), a community high in Bacteroides ("Bacteroides"), and a mixed community ("Mixed") that did not fall into one of the other three enterotypes but instead consisted of a varied combination of bacteria, including among others Akkermansia, Collinsela, Prevotella, and/or Bacteroides.
Stool Microbiota Composition Change During Synbiotic Treatment	Five weeks	The stool microbiome composition will be analyzed through next generation sequencing and quantitative polymerase chain reaction. Overall bacterial composition change is reported here, as change in enterotype from before synbiotic treatment to after synbiotic treatment, for all subjects. Enterotypes were organized into four categories for analysis: a community high in Prevotella ("Prevotella"), a community high in Bifidobacterium ("Bifidobacterium"), a community high in Bacteroides ("Bacteroides"), and a mixed community ("Mixed") that did not fall into one of the other three enterotypes but instead consisted of a varied combination of bacteria, including among others Akkermansia, Collinsela, Prevotella, and/or Bacteroides.

Secondary Outcome Measures

Name	Time	Method
Serum Immune Profile Change During Prebiotic Only Treatment	Five weeks	Luminex technology will be used to determine a serum immune profile of each participants in response to the study supplement. This profile included assessment of change in percentage of stimulated CD4+ T cells producing intracellular IL-13 before and after Synbiotic treatment ("Post-Synbiotic % IL-13"), and assessment of change in percentage of stimulated CD8+ T cells producing TNF-alpha before and after Prebiotic Only treatment ("Post-Prebiotic % TNF-alpha"). Results are reported here for all subjects regardless of treatment order assignment. Decrease in inflammatory cytokines IL-13 and TNF-alpha is interpreted as a positive outcome.