Intestinal bacteria and metabolites reveal patterns associated with depression in older adults

Researchers uncover clear microbial and metabolic signatures in the courage of older adults with depression, pointing to new measures of mental health therapy targeting individualized microbiota.

study: Multiomics approach identifies gut microbiota variations associated with depression. Image credit: Tatiana Shepeleva / Shutterstock

New research published in the Nature Portfolio Journal Biofilms and microorganisms Revealing significant changes in gut microbiota composition in older Mediterranean adults with overweight/obesity and metabolic syndrome. This finding provides a future research avenue to determine whether the gut microbiota affects the pathophysiology of depression.

background

Depression is a serious mental disorder characterized by a sense of sadness and a lack of interest in long-term activity. An estimated 3.8% of the world's population experiences depression at some point in their lives.

Several social, psychological, lifestyle, and biological factors can lead to the onset of depression. Changes in gut microbiota composition have also been observed in patients with major depressive disorder.

The gut microbiota has been found to affect physical and mental health through the gut brain axis, a complex bidirectional network of neuro, endocrine, immune, and metabolic pathways.

The vagus nerve in the brain sends signals to the gut, and the gut microbiota processes these signals and responds via multiple pathways including activation of stray dogs, immune regulation, inflammatory mediators and production of microbial metabolites. Both inflammatory mediators and microbial metabolites can cross the blood-brain barrier and regulate brain function.

Given the potential link between gut microbial flora and depression development, the current study aims to characterize gut microbial composition and fecal profiles of gut microbial microbial derived metabolites in older Mediterranean adults with metabolic syndrome and depressive symptoms.

Research Design

This study included 400 Mediterranean adults (ages 55-75) who were overweight/obesity and metabolic syndrome. Depression status was defined as Beck Depression Inventory II (BDI-II) score ≥20 (indicating moderate to severe symptoms) or current antidepressant use.

The composition of the gut microbiota of participants was characterized by 16S ribosomal RNA sequencing, and fecal metabolite profiles were assessed using liquid chromatography tandem mass spectrometry. Analyses adjusted for diet, smoking, physical activity, and other covariates.

Survey results

The researchers categorized 69 participants into the depression group (DG) and 331 into the reference group (RG).

They observed significant differences in the abundance and diversity of the gut microbiota between depression and reference groups. Specifically, we identified eight bacterial genera containing them. Acidominococcus and Megas Fara (Abundant depression) Christensenelaceae R-7 Group (Depleted due to depression). This was different and abundant across groups.

They performed predictive functional profiling of microbial communities and identified pathways that were significantly associated with depression. These pathways were associated with type II diabetes, bile secretion, secondary metabolite biosynthesis, carbohydrate metabolism, and amino acid metabolism. Notably, predicted confusion in the tryptophan metabolic pathway was not consistent with the detected fecal metabolites.

By performing metabolic analysis of fecal samples, they identified metabolites primarily of lipids, organic acids, and benzenoid 15. Some of these metabolites were significantly associated with the properties of intestinal microorganisms.

The importance of research

This study is the first to simultaneously utilize uninhibited fecal metabolites and microbial ribosomal RNA sequencing to determine the association between the gut microbiota and depression.

This study identifies eight bacterial genera and 15 fecal metabolites that are significantly associated with depression. Reveal specific bacteria genus including Streptococcus, Acidominococcusand Megas FaraAlthough there was a significant amount of participants with depression, Christensenelaceae R-7 Group Other SCFA-producing taxa have decreased.

Streptococcus It is usually associated with the oral microbiota, and its presence in the gut may indicate a breakdown of the oral microbial axis. Promotion Streptococcus Levels were potentially associated with depressive symptoms via destruction of cerotonergic signaling and neuroinflammation.

Genus Acidominococcus It is associated with the production of glutamate, an important excitatory neurotransmitter in the brain. Overproduction of glutamate can lead to excitotoxicity, neuroinflammation, and pathophysiology of depression. These observations justify the link between this genus and depression.

Genus Megas Fara It is associated with the production of propionate salts, and this overproduction of short-chain fatty acids is known to destroy the gut brain axis by altering signaling pathways and promoting proinflammatory conditions.

Among the depression-related metabolites identified in this study, the short-chain fatty acid Valeric acid showed significant enrichment in participants with depression. In animal studies, elevated silver acid levels are associated with changes in gut microbiome composition and changes in gut brain axis.

Reduced proline metabolism in participants with depression is an important precursor of glutamic acid. Reduced proline metabolism may limit the availability of glutamate, potentially affecting neuroplasticity and mood regulation. These findings collectively show that bacterial-derived metabolites may affect the association between gut microbiome and depression.

This study did not find any significant differences in gut microbiota composition or metabolite profiles among participants who consumed and did not consume antidepressants. These findings indicate that antidepressants do not significantly affect the gut microbiota. Another possibility is that depression-related gut microbiota changes persist despite pharmacological treatment.

Limitations include cross-sectional design that prevents causal conclusions and prevents reliance on BDI-II questionnaires. This is a screening tool rather than a clinical diagnosis of depression. The study also did not take into account the consistency of stools that could affect microbiota composition.

As the researchers stated, future research should be explored Effectiveness of Gut microbiota targeted therapy in patients with depression, especially those who do not respond to antidepressants.