The gut-microbiota-brain axis in a Spanish population in the aftermath of the COVID-19 pandemic: microbiota composition linked to anxiety, trauma, and depression profiles

Abstract

The prevalence of anxiety and depression soared following the COVID-19 pandemic. To effectively treat these conditions, a comprehensive understanding of all etiological factors is needed. This study investigated fecal microbial features associated with mental health outcomes (symptoms of anxiety, depression, or posttraumatic stress disorder (PTSD)) in a Spanish cohort in the aftermath of the COVID-19 pandemic. Microbial communities from stool samples were profiled in 198 individuals who completed validated, self-report questionnaires. 16S ribosomal RNA gene V3-4 amplicon sequencing was performed. Microbial diversity and community structure were analyzed, together with relative taxonomic abundance. In our cohort of N=198, 17.17% reported depressive symptoms, 37.37% state anxiety symptoms, 40.90% trait anxiety symptoms, and 8.08% PTSD symptoms, with high levels of comorbidity. Individuals with trait anxiety had lower Simpson’s diversity. Fusicatenibacter saccharivorans was reduced in individuals with comorbid PTSD + depression + state and trait anxiety symptoms, whilst an expansion of Proteobacteria and depletion of Synergistetes phyla were noted in individuals with depressive symptoms. The relative abundance of Anaerostipes was positively correlated with childhood trauma, and higher levels of Turicibacter sanguinis and lower levels of Lentisphaerae were found in individuals who experienced life-threatening traumas. COVID-19 infection and vaccination influenced the overall microbial composition and were associated with distinct relative taxonomic abundance profiles. These findings will help lay the foundation for future studies to identify microbial role players in symptoms of anxiety, depression, and PTSD and provide future therapeutic targets to improve mental health outcomes.

Mixed Depression in the Post-COVID-19 Syndrome: Correlation between Excitatory Symptoms in Depression and Physical Burden after COVID-19

“…Furthermore, our study reported that the familial transmission observed in the affective disorder also applies to the subgroup of those affected by the post-COVID-19 syndrome. Regarding physical symptoms, our results are in line with those documenting a relationship between depression and fatigue and pain in COVID-19 survivors [ 10 , 16 ], and those documenting alterations in microbiome [ 17 ]. In addition to these studies, we reported higher rates of cough, headache, anosmia, dysgeusia, red eyes, low vision, syncope, vertigo, Sjogren’s syndrome, dyspnea, chest pain, sore throat, rhinitis, and lack of appetite in subjects with depression.…”

“…Mazza et al [ 10 , 16 ] also found a high level of fatigue and pain in COVID-19 survivors with depression. Post-COVID-19 syndrome’s associated depression has been also related to microbiome alteration [ 17 ] and higher incidence of gastrointestinal symptoms such as heartburn, constipation, diarrhea, and abdominal pain [ 18 ]. However, the reliability of the aforementioned studies is hampered by small sample sizes and the narrow range of post-COVID-19 syndrome’s symptoms that have been assessed.…”

Integrated 16S rRNA sequencing and metagenomics insights into microbial dysbiosis and distinct virulence factors in inflammatory bowel disease

“…Enterococcus also stimulates apoptosis of intestinal epithelial cells deprived of the protective mucus layer (Golińska et al, 2013 ) and might contribute to the pathway of “bacterial invasion of epithelial cells.” Meanwhile, the Christensenellaceae R-7 group could be the cause of the increased Escherichia-Shigella levels and was also identified as a biomarker in the feces of healthy participants with high abundance (Cai et al, 2023 ). Fusicatenibacter, Faecalibacterium , and Ruminococcus are healthy gut-associated butyrate-producing bacteria known to be beneficial to host immunity (Maruyama et al, 2022 ; Malan-Müller et al, 2023 ), and butyrate is an important regulator that reduces mucosal inflammation and strengthens the epithelial defense barrier (Canani et al, 2011 ). Furthermore, Holdemanella was positively correlated with C18-3OH, a compound known for its anti-inflammatory properties (Pujo et al, 2021 ).…”

Alterations in microbiota of patients with COVID‐19: implications for therapeutic interventions

“…Pathogenic microbiota produce harmful substances and inflammatory molecules in the gut, which then infiltrate into the brain, eventually causing neuroinflammation and cognitive impairment 114 . Gut–brain axis regulation is also reflected in some people with mental health disorders such as anxiety and depression, which are often accompanied by an abnormal abundance of gut microbiota, suggesting that intestinal flora disorder may also play a role in COVID‐19‐related anxiety and depression 115,116 . The potential causal relationship and processes between SARS‐CoV‐2 and gut microbiota alterations are shown in Figure 3.…”