Lower serum levels of IL-1β and IL-6 cytokines in adolescents with anorexia nervosa and their association with gut microbiota in a longitudinal study

Abstract

IntroductionAnorexia nervosa (AN) is an often chronic and debilitating psychiatric disease whose etiology is not completely understood. Recently, a potential role of inflammation has emerged in other psychiatric diseases, such as depression, PTSD and schizophrenia. The first results in adults with AN seemed to confirm a low-grade proinflammatory state until recent studies presented more differential findings. Studying adolescents with a shorter illness duration and fewer confounding factors might help elucidate the role of inflammation in the underlying pathophysiology of AN; however, the few available studies in adolescents remain ambiguous, and no longitudinal data are available in this age range.MethodsWe examined the proinflammatory cytokines Tumor Necrosis Factor-alpha (TNF-α), Interleukin (IL)-1β, IL-6, IL-15, and the cytokine-receptor IL-6 Receptor alpha (IL-6 Rα) in the serum of twenty-two hospitalized female adolescent patients with AN longitudinally at admission and discharge and compared their results to nineteen healthy controls (HC). We also collected clinical data and stool samples that were analyzed with 16S rRNA amplicon sequencing to explore potential influencing factors of cytokine changes.ResultsTNF-α serum levels were significantly elevated in patients with AN at admission, while IL-1β and IL-6 levels were lower at admission and discharge than in HC. After treatment, we also found significantly elevated levels of IL-6 Rα compared to HC, while IL-15 did not show significant changes. Exploratory analyses revealed positive associations of cytokine and genus-level changes between admission and discharge for IL-1β (Bacteroides) and IL-15 (Romboutsia), and negative associations for IL-15 (Anaerostipes) and TNF-α (uncultured Lachnospiraceae).ConclusionWe confirmed a previous finding of elevated levels of TNF-α also in adolescents with AN; however, the reduced IL-1β and IL-6 levels differed from the mostly increased levels found in adults. A mixed pro- and anti-inflammatory state appears to be present in adolescents, potentially due to their shorter illness duration. The gut microbiota, with its regulatory function on cytokine production, might play a role in mediating these inflammatory processes in AN and could offer targets for new therapeutic approaches.

Longitudinal changes in brain-derived neurotrophic factor (BDNF) but not cytokines contribute to hippocampal recovery in anorexia nervosa above increases in body mass index

“…In the consideration of our findings, it is important to note that concentrations of IL-6, TNF-α, and BDNF were not found to be different between acAN-TP1 and HC, partially contrasting with the previous literature (Dalton et al, 2018;Keeler et al, 2022) but aligning with more recent research findings that account for potentially confounding variables (e.g. smoking status, psychotropic medication; Keeler et al, 2021a;Specht et al, 2022). Moreover, concentrations of IL-6 did not decrease with weight restoration, contrasting with a prior study (Dalton et al, 2020).…”

The Role of the Gut Microbiota in Anorexia Nervosa in Children and Adults—Systematic Review

“…In their study on 22 patients with AN, Specht et al (2022) observed an inverse relationship between changes in proinflammatory cytokines and specific microbial taxa possessing well-documented anti-inflammatory properties, such as Lachnospiraceae and Anaerostipes . Notably, the increased abundance of Lachnospiraceae during short-term weight recovery could potentially contribute to the reduction in TNF-α levels [ 106 ]. Previous research has linked Lachnospiraceae to favourable effects on cardiovascular risk factors and anti-inflammatory effects in the context of inflammatory bowel disease [ 107 , 108 ].…”

“…These findings collectively suggest the potential for a bidirectional interdependence between gut microbiota and inflammation in individuals with AN. The observed associations between specific microbial taxa and proinflammatory processes may hold valuable insights into the intricate relationship between gut microbiota composition and inflammatory states in AN [ 106 ].…”

Longitudinal analysis of the gut microbiome in adolescent patients with anorexia nervosa: microbiome-related factors associated with clinical outcome

“… 50 , 51 Patients with AN are thought to have chronic low-grade inflammation of unknown origin (meta-analysis by 52 ); however, recent findings are more diverse and show variable dysregulation of the immunologic state. 53 , 54 AN is also associated with an increased rate of autoimmune diseases, especially Crohn’s disease and celiac disease. 55 , 56 Therefore, the immunomodulatory effects of these taxa might be important for their mechanistic role in AN outcomes.…”