Bile acids and bile acid activated receptors in the treatment of Covid-19

Fiorucci, Stefano; Urbani, Ginevra; Biagioli, Michele; Sepe, Valentina; Distrutti, Eleonora; Zampella, Angela

doi:10.1016/j.bcp.2023.115983

Cited by 6 publications

(6 citation statements)

References 98 publications

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“…We found that schizophrenia-related genes share the enrichment pathway for bile acid metabolism. Bile acids prevent the binding of spike protein with angiotensin-converting enzyme II (ACE2) and modulate the expression of ACE2, suggesting the protective role [42]. Our study also showed that COVID-19 vaccination reduced risks of schizophrenia.…”

Section: Discussionsupporting

confidence: 53%

Psychiatric adverse events following COVID-19 vaccination: a population-based cohort study in Seoul, South Korea

Kim,

Choi

et al. 2024

Mol Psychiatry

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Evidence has suggested an increased risk of psychiatric manifestations following viral infections including coronavirus disease-2019 (COVID-19). However, psychiatric adverse events (AEs) after COVID-19 vaccination, which were documented in case reports and case series, remain unclear. This study is aimed to investigate the psychiatric AEs after COVID-19 vaccination from a large population-based cohort in Seoul, South Korea. We recruited 50% of the Seoul-resident population randomly selected from the Korean National Health Insurance Service (KNHIS) claims database on 1, January, 2021. The included participants (n = 2,027,353) from the Korean National Health Insurance Service claims database were divided into two groups according to COVID-19 vaccination. The cumulative incidences per 10,000 of psychiatric AEs were assessed on one week, two weeks, one month, and three months after COVID-19 vaccination. Hazard ratios (HRs) and 95% Confidence interval (CIs) of psychiatric AEs were measured for the vaccinated population. The cumulative incidence of depression, anxiety, dissociative, stress-related, and somatoform disorders, sleep disorders, and sexual disorders at three months following COVID-19 vaccination were higher in the vaccination group than no vaccination group. However, schizophrenia and bipolar disorders showed lower cumulative incidence in the vaccination group than in the non-vaccinated group. Depression (HR [95% CI] = 1.683 [1.520–1.863]), anxiety, dissociative, stress-related, and somatoform disorders (HR [95% CI] = 1.439 [1.322–1.568]), and sleep disorders (HR [95% CI] = 1.934 [1.738–2.152]) showed increased risks after COVID-19 vaccination, whereas the risks of schizophrenia (HR [95% CI] = 0.231 [0.164–0.326]) and bipolar disorder (HR [95% CI] = 0.672 [0.470–0.962]). COVID-19 vaccination increased the risks of depression, anxiety, dissociative, stress-related, and somatoform disorders, and sleep disorders while reducing the risk of schizophrenia and bipolar disorder. Therefore, special cautions are necessary for administering additional COVID-19 vaccinations to populations vulnerable to psychiatric AEs.

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Section: Discussionsupporting

confidence: 53%

Psychiatric adverse events following COVID-19 vaccination: a population-based cohort study in Seoul, South Korea

Kim,

Choi

et al. 2024

Mol Psychiatry

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“…Although the etiology of long COVID is not yet entirely understood, dysregulated metabolism may play a role. Lipid metabolism is highly influenced by COVID-19 [43,44], and bile acids are also dysregulated [45], with existing acute-stage treatments only partially able to modulate these lipid metabolism effects [46]. Therefore, these concepts further reinforce the theorical need of trialing lactoferrin in this condition.…”

Section: Discussionmentioning

confidence: 98%

Persisting Gastrointestinal Symptoms in Children with SARS-CoV-2: Temporal Evolution over 18 Months and Possible Role of Lactoferrin

Mariani,

Rainaldi,

Dall’Ara

et al. 2024

Children

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Background and aim: Persisting gastrointestinal symptoms are reported to be relatively common in children with long COVID; however, their detailed characterization and long-term outcomes have not yet been described. Methods: We performed a retrospective study aiming to investigate the temporal evolution of gastrointestinal symptoms in children with SARS-CoV-2, from acute infection to 18-months follow-up. To further investigate possible therapeutic strategies, we evaluated the role of lactoferrin in improving gastrointestinal symptoms in these children, compared with those not treated. Results: A total of 1224 patients (47.7% females) were included. Of these participants, 246 (19.8%) were vaccinated and 143 (11.5%) presented with comorbidities. A total of 175 patients (14.1%) presented gastrointestinal symptoms during acute infection, 54 (4.4%) at three months, 23 (1.9%) at six months, 6 (3.3%) at twelve months, and 2 (2.3%) at eighteen months follow-up. At six months follow-up, children who were treated with 3 months oral lactoferrin had less persisting symptoms compared to those who did not receive lactoferrin, although this difference was not statistically significant (three patients (25%) in the lactoferrin group vs. fourteen patients (33.3%) not treated, p = 0.73), probably due to the low number of patients with persisting GI symptoms. Conclusions: GI symptoms are relatively common during acute SARS-CoV-2 infection in children, and a non-negligible proportion of these children reported persisting symptoms for up to 12–18 months after the acute infection. In addition, we found a trend even if statistically nonsignificant toward faster improvement of persisting gastrointestinal symptoms in children with long COVID treated with lactoferrin. Despite the limitations relating to the present study’s design, given the significant burden of gastrointestinal symptoms in children with long COVID, our findings provide the basis to perform a prospective, placebo-controlled study.

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“…Bile acids (BAs) have been proposed to modulate SARS-CoV-2’s entry into host cells through FXR and GPBAR1 by regulating ACE2 expression in various tissues [ 49 ]. Additionally, BAs can suppress intestinal dendritic cell (DC) differentiation and activation via FXR [ 62 , 63 ], and regulate inflammatory responses through TGR5 activation, leading to decreased IFN-γ, IL-1β, IL-6, and TNF-α, and increased IL-10 [ 42 ].…”

Section: Discussionmentioning

confidence: 99%

“…The cellular entry of SARS-CoV-2 is facilitated by the spike protein binding to the angiotensin-converting enzyme 2 (ACE2) receptor. Interestingly, BAs may influence ACE2 expression in various tissues through their interaction with FXR and GPBAR1 [ 49 ]. Brevini et al demonstrated that biliary organoids cultured in the presence of cholic acid (CDCA), a primary bile acid, expressed ACE2.…”

Section: Introductionmentioning

confidence: 99%

Modulatory Roles of AHR, FFAR2, FXR, and TGR5 Gene Expression in Metabolic-Associated Fatty Liver Disease and COVID-19 Outcomes

Buchynskyi,

Oksenych,

Kamyshna

et al. 2024

Viruses

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Metabolic-associated fatty liver disease (MAFLD) is a risk factor for severe COVID-19. This study explores the potential influence of gut hormone receptor and immune response gene expression on COVID-19 outcomes in MAFLD patients. Methods: We investigated gene expression levels of AHR, FFAR2, FXR, and TGR5 in patients with MAFLD and COVID-19 compared to controls. We examined associations between gene expression and clinical outcomes. Results: COVID-19 patients displayed altered AHR expression, potentially impacting immune response and recovery. Downregulated AHR in patients with MAFLD correlated with increased coagulation parameters. Elevated FFAR2 expression in patients with MAFLD was linked to specific immune cell populations and hospital stay duration. A significantly lower FXR expression was observed in both MAFLD and severe COVID-19. Conclusion: Our findings suggest potential modulatory roles for AHR, FFAR2, and FXR in COVID-19 and MAFLD.

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Bile acids and bile acid activated receptors in the treatment of Covid-19

Cited by 6 publications

References 98 publications

Psychiatric adverse events following COVID-19 vaccination: a population-based cohort study in Seoul, South Korea

Psychiatric adverse events following COVID-19 vaccination: a population-based cohort study in Seoul, South Korea

Persisting Gastrointestinal Symptoms in Children with SARS-CoV-2: Temporal Evolution over 18 Months and Possible Role of Lactoferrin

Modulatory Roles of AHR, FFAR2, FXR, and TGR5 Gene Expression in Metabolic-Associated Fatty Liver Disease and COVID-19 Outcomes

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