Beneath the surface: unveiling the gut–brain axis in anorexia and depression

Abstract

Anorexia nervosa (AN) and depression are complex conditions with high comorbidity, impacting mental and physical health. Recent research suggests gut microbiota plays a significant role in their development and progression. This correspondence highlights the critical gaps in understanding the gut–brain axis in AN and depression, emphasizing the need for comprehensive research. We discuss recent findings, including altered gut microbiota profiles and inflammatory factors, and identify key areas for future investigation. These include large-scale, multi-center studies to quantify microbiota profiles, mechanistic understanding of gut microbiota alterations, and diagnostic and therapeutic advances using microbiota as biomarkers. Addressing these gaps is crucial for developing effective treatment strategies and improving patient outcomes. By exploring the underlying mechanisms, validating biomarkers, and developing targeted therapies, we can enhance diagnostic accuracy, improve treatment outcomes, and better support patients with AN and depression. This research has the potential to transform the management of these conditions and improve quality of life for those affected.

Level of evidence Low level of evidence as it is a personal opinion.

Correspondence

Anorexia nervosa (AN), a silent killer with a prevalence of around 4 percent in females and 0.3 percent in males, is increasingly impacting younger populations [1]. Characterized by severe restriction of food intake and an intense fear of weight gain, AN often coexists with depression, affecting about 40% of AN patients and compounding its impact on mental and physical health [2]. Mortality rates can be as high as 5%, and patients with AN face a tenfold increased risk of suicide, underscoring the severe consequences of this condition [3]. Recent research has highlighted that gut microbiota may play a significant role in the development and progression of both AN and depression, further complicating the management of these intertwined conditions.

Gut microbiota, the microorganisms residing in the gastrointestinal tract, play essential roles, including amino acid synthesis, neurotransmitter production, and immune response regulation [4]. The gut–brain axis operates through pathways such as the vagus nerve, hypothalamic–pituitary–adrenal (HPA) axis, and microbial metabolites like short-chain fatty acids (SCFAs), which influence brain function and inflammation. Disruptions in these pathways contribute to the pathology of anorexia nervosa (AN) and depression (Cryan 2012, Foster 2017) [5, 6]. Specific microbiota such as Coprococcus, Eggerthella, and Subdoligranulum have been associated with depression [4, 5]. These microbes influence inflammatory cytokines, which can cross the blood–brain barrier and affect neurotransmitter levels, contributing to mood dysregulation [6]. In a nutshell, gut microbiota is often involved in the development of depression which can exacerbate the inflammatory factors and is often accompanied by AN. Gut dysbiosis, characterized by reduced diversity and altered bacterial composition, has been associated with increased anxiety, depressive symptoms, and disordered eating behaviors [6, 7]. For instance, alterations in serotonin synthesis due to dysbiosis can exacerbate mood disorders, further complicating the clinical picture of AN [7]. A recent study “Gut microbiota and inflammatory factor characteristics in major depressive disorder patients with anorexia” analyzed this correlation [8]. It concluded that not only C-reactive protein levels were raised in MDA0 (MDD without anorexia) and MDA1 (MDD with anorexia) group, but also MDA1 group revealed lower α-diversity indices (Simpson and Pielou) compared to HC (healthy control), indicating reduced microbial diversity in those with MDD and anorexia. Moreover, β-diversity analysis highlighted elevated levels of Blautia, Enterococcus, and Bifidobacterium MDA1 patients. Thus, specific bacterial genera were correlated with anorexia, depression severity, and CRP levels. For instance, Blautia was positively correlated with AN, HAMD scores, and CRP levels, while Faecalibacterium, Bacteroides, Roseburia, and Parabacteroides were negatively correlated with these factors. These findings suggest that specific bacterial genera could be used as biomarkers to accurately differentiate and diagnose MDD patients with anorexia another 2015 study revealed a similar pattern [9]. A negative association was found between number of observed gut microbiota and greater levels of depression and AN. Moreover, patients with AN exhibited significantly higher levels of the class Bacilli and an unspecified genus within the family Coriobacteriales alongside reduced levels of the class Clostridia and the genera Anaerostipes and Faecalibacterium compared to HC.

Nonetheless, several critical literature gaps persist in the understanding of gut microbiota’s role in anorexia and depression, hindering the development of effective treatment strategies. Addressing these gaps is crucial for advancing both diagnostic and therapeutic approaches in this field:

• 1. Comprehensive data collection While recent studies provide valuable insights, a more extensive analysis of gut microbiota and its interaction with AN and depression is needed. A large-scale, multi-center study could help quantify the prevalence of specific microbiota profiles and their correlation with these conditions, providing a clearer understanding of their impact and guiding effective treatment strategies.

• 2. Mechanistic understanding There is a need for deeper exploration into the mechanistic pathways linking gut microbiota with AN and depression. Research should focus on elucidating how gut microbiota alterations contribute to the development and progression of these disorders, which could lead to targeted interventions and better therapeutic approaches.

• 3. Diagnostic and therapeutic advances Limited research has explored the use of gut microbiota as diagnostic biomarkers for anorexia and depression. Further studies should aim to validate potential biomarkers and develop clinical tools for early detection and personalized treatment based on microbiota profiles as well as assess the long-term effects of microbiota-targeted therapies on patients with AN and depression.

In conclusion, while recent studies provide valuable insights into the relationship between gut microbiota, anorexia, and depression, significant gaps in the literature remain. Addressing these gaps is crucial to advancing our understanding and treatment of these complex conditions. Comprehensive research is needed to explore the underlying mechanisms, validate potential biomarkers, and develop targeted therapies. By focusing on these areas, we can enhance diagnostic accuracy, improve treatment outcomes, and better support patients. Let us advance this research to transform the management of anorexia and depression and improve the quality of life for those affected.

Author contributions

F.S: Conceptualization, Data curation, Formal analysis, Methodology, Supervision, Writing – original draft, Writing – review & editing. Z.A: Data curation, Formal analysis, Writing – original draft, Writing – review & editing. M.A: Writing – original draft, Writing – review & editing. M.N.S: Writing – original draft, Writing – review & editing; J.I: Writing – original draft, Writing – review & editing; A.J: Writing – original draft, Writing – review & editing.

Funding

The authors received no funding.

Availability of data and materials

No datasets were generated or analysed during the current study.

Declarations

Competing interests

The authors declare no competing interests.