Citation: Xu, J.; Landberg, R.; Lavebratt, C.; Bulik, C.M.; Landén, M.; Nilsson, I.A.K. Plasma Concentrations of Short-Chain Fatty Acids in Active and Recovered Anorexia Nervosa. Nutrients 2022, 14, 5247. https://doi.org/10.3390/ nu14245247 Academic Editors: Maria Sofia Cattaruzza, Francesca Gallè and Federica Valeriani Received: 15 November 2022 Accepted: 7 December 2022 Published: 9 December 2022 Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affil- iations. Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). nutrients Article Plasma Concentrations of Short-Chain Fatty Acids in Active and Recovered Anorexia Nervosa Jingjing Xu 1,2 , Rikard Landberg 3 , Catharina Lavebratt 1,2 , Cynthia M. Bulik 4,5,6,7 , Mikael Landén 5,8,† and Ida A. K. Nilsson 1,2,4, * ,† 1 Department of Molecular Medicine and Surgery, Karolinska Institutet, 171 76 Stockholm, Sweden 2 Center for Molecular Medicine, Karolinska University Hospital, 171 76 Stockholm, Sweden 3 Department of Biology and Biological Engineering, Food and Nutrition Science, Chalmers University of Technology, 412 96 Gothenburg, Sweden 4 Centre for Eating Disorders Innovation, Karolinska Institutet, 171 77 Stockholm, Sweden 5 Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, 171 77 Stockholm, Sweden 6 Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA 7 Department of Nutrition, University of North Carolina at Chapel Hill, Chapel Hill, NC 27516, USA 8 Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, 405 30 Gothenburg, Sweden * Correspondence: ida.nilsson@ki.se; Tel.: +46-7086-31361 † These authors contributed equally to this work. Abstract: Anorexia nervosa (AN) is one of the most lethal psychiatric disorders. To date, we lack adequate knowledge about the (neuro)biological mechanisms of this disorder to inform evidence- based pharmacological treatment. Gut dysbiosis is a trending topic in mental health, including AN. Communication between the gut microbiota and the brain is partly mediated by metabolites produced by the gut microbiota such as short-chain fatty acids (SCFA). Previous research has suggested a role of SCFA in weight regulation (e.g., correlations between specific SCFA-producing bacteria and BMI have been demonstrated). Moreover, fecal SCFA concentrations are reported to be altered in active AN. However, data concerning SCFA concentrations in individuals who have recovered from AN are limited. In the present study, we analyzed and compared the plasma concentrations of seven SCFA (acetic-, butyric-, formic-, isobutyric-, isovaleric-, propionic-, and succinic acid) in females with active AN (n = 109), recovered from AN (AN-REC, n = 108), and healthy-weight age-matched controls (CTRL, n = 110), and explored correlations between SCFA concentrations and BMI. Significantly lower plasma concentrations of butyric, isobutyric-, and isovaleric acid were detected in AN as well as AN-REC compared with CTRL. We also show significant correlations between plasma concentrations of SCFA and BMI. These results encourage studies evaluating whether interventions directed toward altering gut microbiota and SCFA could support weight restoration in AN. Keywords: anorexia nervosa; short-chain fatty acids; plasma; BMI 1. Introduction Up to 4% of females and 0.3% of males are estimated to be diagnosed with the psychiatric disorder anorexia nervosa (AN) during their lifetime [1], a disorder with both high mortality (up to 10%) and relapse rates [2–4], illustrative of its severity. Core features of AN are persistent restriction of food intake resulting in severe underweight, fear of gaining weight, persistent behaviors that interfere with weight gain, and a distorted body image or lack of recognition of the seriousness of the low weight [5,6]. Heritability of AN has been established by several twin studies, where 58–70% of the variance in liability has been found to be explained by additive genetic factors [7]. The latest genome-wide association study (GWAS) identified eight loci associated with AN, as well as significant genetic correlations with several other psychiatric disorders and metabolic traits [8]. Environmental and neurobiological factors also contribute to the development and/or maintenance of Nutrients 2022, 14, 5247. https://doi.org/10.3390/nu14245247 https://www.mdpi.com/journal/nutrients