Enhancing pediatric attention-deficit hyperactivity disorder treatment: exploring the gut microbiota effects of French maritime pine bark extract and methylphenidate intervention.

Introduction: The pathogenesis of Attention-Deficit Hyperactivity Disorder (ADHD) is thought to be multifactorial, with a potential role for the bidirectional communication between the gut microbiome and brain development and function. Since the "golden-standard" medication therapy with methylphenidate (MPH) is linked to multiple adverse effects, there is a need for alternative treatment options such as dietary polyphenols. These secondary plant metabolites exert antioxidant and anti-inflammatory effects, but much less is known about their impact on the gut microbiota. Since polyphenols are believed to modulate gut microbial composition, interventions might be advantageous in ADHD therapy. Therefore, intervention studies with polyphenols in ADHD therapy investigating the gut microbial composition are highly relevant. Methods: Besides the primary research questions addressed previously, this study explored a potential prebiotic effect of the polyphenol-rich French Maritime Pine Bark Extract (PBE) compared to MPH and a placebo in pediatric ADHD patients by studying their impact on the gut microbiota via amplicon sequencing of the full length 16S rRNA gene ribosomal subunit (V1-V9). Results: One interesting finding was the high relative abundance of Bifidobacteria among all patients in our study cohort. Moreover, our study has identified that treatment (placebo, MPH and PBE) explains 3.94% of the variation in distribution of microbial taxa (adjusted p-value of 0.011). Discussion: Our small sample size (placebo: n = 10; PBE: n = 13 and MPH: n = 14) did not allow to observe clear prebiotic effects in the patients treated with PBE. Notwithstanding this limitation, subtle changes were noticeable and some limited compositional changes could be observed. Clinical Trial Registration: doi: 10.1186/S13063-017-1879-6.

Increasing pulse pressure ex vivo, mimicking acute physical exercise, induces smooth muscle cell-mediated de-stiffening of murine aortic segments.

The mechanisms by which physical activity affects cardiovascular function and physiology are complex and multifactorial. In the present study, cardiac output during rest or acute physical activity was simulated in isolated aortic segments of healthy C57BL/6J wild-type mice. This was performed using the Rodent Oscillatory Tension Set-up to study Arterial Compliance (ROTSAC) by applying cyclic stretch of different amplitude, duration and frequency in well-controlled and manageable experimental conditions. Our data show that vascular smooth muscle cells (VSMCs) of the aorta have the intrinsic ability to "de-stiffen" or "relax" after periods of high cyclic stretch and to "re-stiffen" slowly thereafter upon return to normal distension pressures. Thereby, certain conditions have to be fulfilled: 1) VSMC contraction and repetitive stretching (loading/unloading cycles) are a prerequisite to induce post-exercise de-stiffening; 2) one bout of high cyclic stretch is enough to induce de- and re-stiffening. Aortic de-stiffening was highly dependent on cyclic stretch amplitude and on the manner and timing of contraction with probable involvement of focal adhesion phosphorylation/activation. Results of this study may have implications for the therapeutic potential of regular and acute physical activity and its role in the prevention and/or treatment of cardiovascular disease.