A Randomized Trial of Inspiratory Training in Children and Adolescents With Obesity.

Introduction: Children with obesity suffer excess dyspnea that contributes to sedentariness. Developing innovative strategies to increase exercise tolerance and participation in children with obesity is a high priority. Because inspiratory training (IT) has reduced dyspnea, we sought to assess IT in children with obesity. Methods: We conducted a 6-week randomized IT trial involving 8- to 17-year-olds with obesity. Participants were randomized 1:1 to either high [75% of maximal inspiratory pressure (MIP)] or low resistance control (15% of MIP) three times weekly. Assessments included adherence, patient satisfaction, and changes in inspiratory strength and endurance, dyspnea scores and total activity level. Results: Among 27 randomized, 24 (89%) completed the intervention. Total session adherence was 72% which did not differ between treatment groups. IT was safe, and more than 90% felt IT benefitted breathing and general health. IT led to a mean improvement (95% CI) in inspiratory strength measured by MIP of 10.0 cm H2O (-3.5, 23.6; paired t-test, p = 0.139) and inspiratory endurance of 8.9 (1.0, 16.8; paired t-test, p = 0.028); however, there was no significant difference between high- and low-treatment groups. IT led to significant reductions in dyspnea with daily activity (p < 0.001) and in prospectively reported dyspnea during exercise (p = 0.024). Among the high- versus low-treatment group, we noted a trend for reduced dyspnea with daily activity (p = 0.071) and increased daily steps (865 vs. -51, p = 0.079). Discussion: IT is safe and feasible for children with obesity and holds promise for reducing dyspnea and improving healthy activity in children with obesity. Breathe-Fit trial NCT05412134.

Interplay between particle size and microbial ecology in the gut microbiome.

Physical particles can serve as critical abiotic factors that structure the ecology of microbial communities. For non-human vertebrate gut microbiomes, fecal particle size (FPS) has been known to be shaped by chewing efficiency and diet. However, little is known about what drives FPS in the human gut. Here, we analyzed FPS by laser diffraction across a total of 76 individuals and found FPS to be strongly individualized. Surprisingly, a behavioral intervention with 41 volunteers designed to increase chewing efficiency did not impact FPS. Dietary patterns could also not be associated with FPS. Instead, we found evidence that mammalian and human gut microbiomes shaped FPS. Fecal samples from germ-free and antibiotic-treated mice exhibited increased FPS relative to colonized mice. In humans, markers of longer transit time were correlated with smaller FPS. Gut microbiota diversity and composition were also associated with FPS. Finally, ex vivo culture experiments using human fecal microbiota from distinct donors showed that differences in microbiota community composition can drive variation in particle size. Together, our results support an ecological model in which the human gut microbiome plays a key role in reducing the size of food particles during digestion, and that the microbiomes of individuals vary in this capacity. These new insights also suggest FPS in humans to be governed by processes beyond those found in other mammals and emphasize the importance of gut microbiota in shaping their own abiotic environment.

Ecological memory of prior nutrient exposure in the human gut microbiome.

Many ecosystems have been shown to retain a memory of past conditions, which in turn affects how they respond to future stimuli. In microbial ecosystems, community disturbance has been associated with lasting impacts on microbiome structure. However, whether microbial communities alter their response to repeated stimulus remains incompletely understood. Using the human gut microbiome as a model, we show that bacterial communities retain an "ecological memory" of past carbohydrate exposures. Memory of the prebiotic inulin was encoded within a day of supplementation among a cohort of human study participants. Using in vitro gut microbial models, we demonstrated that the strength of ecological memory scales with nutrient dose and persists for days. We found evidence that memory is seeded by transcriptional changes among primary degraders of inulin within hours of nutrient exposure, and that subsequent changes in the activity and abundance of these taxa are sufficient to enhance overall community nutrient metabolism. We also observed that ecological memory of one carbohydrate species impacts microbiome response to other carbohydrates, and that an individual's habitual exposure to dietary fiber was associated with their gut microbiome's efficiency at digesting inulin. Together, these findings suggest that the human gut microbiome's metabolic potential reflects dietary exposures over preceding days and changes within hours of exposure to a novel nutrient. The dynamics of this ecological memory also highlight the potential for intra-individual microbiome variation to affect the design and interpretation of interventions involving the gut microbiome.