Background: N-acetylaspartate (NAA) is synthesized only by neurons and is involved in neuronal metabolism and axonal myelination. NAA is the strongest signal on brain magnetic resonance spectroscopy, and its concentration have been associated with cognitive dysfunction in neurodegenerative diseases, obesity, and type 2 diabetes (T2D). Materials and Methods: We explored the impact of obesity and T2D on circulating NAA as well as the impact of bariatric surgery and antidiabetic treatments. We developed an LC-MS method for the accurate measurements of fasting plasma NAA levels in 505 subjects (156 subjects with normal glucose tolerance, 24 subjects with impaired glucose tolerance, and 325 patients with T2D) to examine the associations of NAA with obesity and dysglycemia. To validate cross-sectional findings, plasma NAA was measured 6 months after Roux-en-Y Gastric Bypass (RYGB) in 55 morbidly obese subjects, and after 1 year of antidiabetic treatment (with dapagliflozin, exenatide, or dapagliflozin plus exenatide) in 192 T2D patients. Results: In the whole population, NAA was associated with age (r = 0.31, p < 0.0001) and BMI (r = −0.20, p < 0.0001). Independently of age and BMI, NAA was reciprocally related to HbA1c and fasting plasma glucose (partial r = −0.13, both p = 0.01). Surgically-induced weight loss raised NAA (by 18 nmol/L on average, p < 0.02). Glucose lowering treatment increased NAA in proportion to the drop in HbA1c (r = 0.31, p < 0.0001) regardless of the agent used. Conclusions: Circulating NAA concentrations are modulated by age, obesity, and glycemic control. Whether they may mark for the corresponding metabolic effects on brain function remains to be established by joint measurements of spectroscopic signal and cognitive function.

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IntroductionShort-chain fatty acids (SCFAs) are the main by-products of microbial fermentations occurring in the human intestine and are directly involved in the host’s physiological balance. As impaired gut concentrations of acetic, propionic, and butyric acids are often associated with systemic disorders, the administration of SCFA-producing microorganisms has been suggested as attractive approach to solve symptoms related to SCFA deficiency.MethodsIn this research, nine probiotic strains (Bacillus clausii NR, OC, SIN, and T, Bacillus coagulans ATCC 7050, Bifidobacterium breve DSM 16604, Limosilactobacillus reuteri DSM 17938, Lacticaseibacillus rhamnosus ATCC 53103, and Saccharomyces boulardii CNCM I-745) commonly included in commercial formulations were tested for their ability to secrete SCFAs by using an improved protocol in high-performance liquid chromatography coupled to tandem mass spectrometry (HPLC-MS-MS).ResultsThe developed method was highly sensitive and specific, showing excellent limits of detection and quantification of secreted SCFAs. All tested microorganisms were shown to secrete acetic acid, with only B. clausii and S. boulardii additionally able to produce propionic and butyric acids. Quantitative differences in the secretion of SCFAs were also evidenced.DiscussionThe experimental approach described in this study may contribute to the characterization of probiotics as SCFA-producing organisms, a crucial stage toward their application to improve SCFA deficiency.

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