Altered gut microbiota in female mice with persistent low body weights following removal of post-weaning chronic dietary restriction

• Published in: Genome medicine 2016-10, Vol.8 (1), p.103-103, Article 103
• Main Authors: Chen, Jun, Toyomasu, Yoshitaka, Hayashi, Yujiro, Linden, David R, Szurszewski, Joseph H, Nelson, Heidi, Farrugia, Gianrico, Kashyap, Purna C, Chia, Nicholas, Ordog, Tamas
• Format: Article
• Language: English
• Subjects: Animals; Anorexia Nervosa - genetics; Anorexia Nervosa - microbiology; Anorexia Nervosa - physiopathology; Caloric Restriction; Development and progression; Failure to thrive; Feeding Behavior; Female; Gastrointestinal Microbiome; Gastrointestinal Tract - microbiology; Genetic aspects; Growth factors; Health aspects; Mice; Mice, Inbred BALB C; Microbiota (Symbiotic organisms); Phylogeny; Polymerase Chain Reaction; RNA, Ribosomal, 16S - genetics; Weaning; Weight Loss - genetics
• ISSN: 1756-994X; 1756-994X
• DOI: 10.1186/s13073-016-0357-1

Nutritional interventions often fail to prevent growth failure in childhood and adolescent malnutrition and the mechanisms remain unclear. Recent studies revealed altered microbiota in malnourished children and anorexia nervosa. To facilitate mechanistic studies under physiologically relevant conditions, we established a mouse model of growth failure following chronic dietary restriction and examined microbiota in relation to age, diet, body weight, and anabolic treatment. Four-week-old female BALB/c mice (n = 12/group) were fed ad libitum (AL) or offered limited food to abolish weight gain (LF). A subset of restricted mice was treated with an insulin-like growth factor 1 (IGF1) analog. Food access was restored in a subset of untreated LF (LF-RF) and IGF1-treated LF mice (TLF-RF) on day 97. Gut microbiota were determined on days 69, 96-99 and 120 by next generation sequencing of the V3-5 region of the 16S rRNA gene. Microbiota-host factor associations were analyzed by distance-based PERMANOVA and quantified by the coefficient of determination R for age, diet, and normalized body weight change (Δbwt). Microbial taxa on day 120 were compared following fitting with an overdispersed Poisson regression model. The machine learning algorithm Random Forests was used to predict age based on the microbiota. On day 120, Δbwt in AL, LF, LF-RF, and TLF-RF mice was 52 ± 3, -6 ± 1*, 40 ± 3*, and 46 ± 2 % (*, P