Kuljeet K. Chohan Bharat Duggal https://orcid.org/0009-0002-6179-6594


Introduction: Depression is a debilitating mental health condition. Although the underlying pathophysiology of depression is poorly understood, emerging evidence suggests that the gut-brain-immune axis may contribute to depressive symptoms. Recent literature has established that depression is associated with systemic low-grade inflammation. According to the leaky-gut hypothesis, this systemic inflammation is thought to be caused by increased permeability—a by-product of mucosal inflammation. Accordingly, some research has demonstrated that fecal calprotectin (FC)—a marker of mucosal inflammation—is positively associated with depressive symptoms. However, with some research showing no correlation between the two, the literature has a lack of consensus on the topic. The aim of the current systematic review was to clarify the association between FC and depression.

Methods: A search was conducted in Ovid MEDLINE, Embase, and APA PsycInfo using MeSH terms related to fecal calprotectin and depression. All English studies with human participants were screened for eligibility by two individual raters, excluding case studies and review papers. Selected articles were subsequently used in the data extraction to look for relevant study characteristics and their findings regarding the correlation between fecal calprotectin and depression. Additionally, the JBI tool was used to assess risk of bias.

Results: A total of 7 articles were included in the study, comprising 1184 patients. The review found that there is no consensus on whether calprotectin and depression are correlated; therefore, no evidence suggesting utility of calprotectin as a biomarker of depression was found.

Discussion: Despite the conflicting findings of the study, there is still some evidence to suggest that calprotectin could be useful as a biomarker. Some of the included studies found that the time of sample collection in relation to the ranking of depression symptoms has an effect on the degree of correlation.

Conclusion: This study found that fecal calprotectin is a weak biomarker of depression and is impractical in the general population due to the collection method. Alternatives include serum calprotectin and markers of neuroinflammation. Other studies looking at the role of salivary biomarkers in depression may prove to be promising.

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