Dietary Modulation of Gut Microbiota Contributes to Alleviation of Both Genetic and Simple Obesity in Children

Abstract

Gut microbiota has been implicated as a pivotal contributing factor in diet-related obesity; however, its role in development of disease phenotypes in human genetic obesity such as Prader–Willi syndrome (PWS) remains elusive. In this hospitalized intervention trial with PWS (n = 17) and simple obesity (n = 21) children, a diet rich in non-digestible carbohydrates induced significant weight loss and concomitant structural changes of the gut microbiota together with reduction of serum antigen load and alleviation of inflammation. Co-abundance network analysis of 161 prevalent bacterial draft genomes assembled directly from metagenomic datasets showed relative increase of functional genome groups for acetate production from carbohydrates fermentation. NMR-based metabolomic profiling of urine showed diet-induced overall changes of host metabotypes and identified significantly reduced trimethylamine N-oxide and indoxyl sulfate, host-bacteria co-metabolites known to induce metabolic deteriorations. Specific bacterial genomes that were correlated with urine levels of these detrimental co-metabolites were found to encode enzyme genes for production of their precursors by fermentation of choline or tryptophan in the gut. When transplanted into germ-free mice, the pre-intervention gut microbiota induced higher inflammation and larger adipocytes compared with the post-intervention microbiota from the same volunteer. Our multi-omics-based systems analysis indicates a significant etiological contribution of dysbiotic gut microbiota to both genetic and simple obesity in children, implicating a potentially effective target for alleviation.Research in contextPoorly managed diet and genetic mutations are the two primary driving forces behind the devastating epidemic of obesity-related diseases. Lack of understanding of the molecular chain of causation between the driving forces and the disease endpoints retards progress in prevention and treatment of the diseases. We found that children genetically obese with Prader–Willi syndrome shared a similar dysbiosis in their gut microbiota with those having diet-related obesity. A diet rich in non-digestible but fermentable carbohydrates significantly promoted beneficial groups of bacteria and reduced toxin-producers, which contributes to the alleviation of metabolic deteriorations in obesity regardless of the primary driving forces.

Application of multivariate statistical techniques in microbial ecology

“…CIA allows each variable set to be analyzed by a different ordination algorithm (Dray et al , 2003a). Co-inertia analysis has been used in several recent studies to reveal relationships between human-associated microbiome and metabolome datasets in the gut of the elderly (Claesson et al , 2012), on the intestinal mucosal surface (McHardy et al , 2013), and in obese subjects (Zhang et al , 2015). …”

“…Thus, it can also be used to assess if multiple ordination techniques applied to the same object-by-variable dataset produce similar results (Bassett et al , 2015). Other examples of PA use are provided in studies by (Claesson et al , 2012), (McHardy et al , 2013), and (Zhang et al , 2015). …”

The human gut microbiome as source of innovation for health: Which physiological and therapeutic outcomes could we expect?

“…It was recently shown that the response to a probiotic mix may be modulated by the initial microbiota configuration, the latter driving the permissivity to fermented food lactic acid bacteria [106,107]. Similarly, work by Chung et al indicates that depending on the presence/absence of specific fiber degraders, the microbiota may be totally irresponsive to specific fibers [108].…”

Integrative Physiology: At the Crossroads of Nutrition, Microbiota, Animal Physiology, and Human Health

“…In a clinical trial on nutritional intervention of genetically obese children with Prader- Willi syndrome, high complex carbohydrates in the diet induced significant changes of the gut microbiota with concomitant weight loss and alleviation of metabolic deteriorations (Zhang et al, 2015). NMR-based metabolomic analysis of the urine samples showed a significant decrease of TMAO concentration.…”