How Toll-like receptors influence Parkinson's disease in the microbiome-gut-brain axis.

Recently, a large number of experimenters have found that the pathogenesis of Parkinson's disease may be related to the gut microbiome and proposed the microbiome-gut-brain axis. Studies have shown that Toll-like receptors, especially Toll-like receptor 2 (TLR2) and Toll-like receptor 4 (TLR4), are key mediators of gut homeostasis. In addition to their established role in innate immunity throughout the body, research is increasingly showing that the Toll-like receptor 2 and Toll-like receptor 4 signaling pathways shape the development and function of the gut and enteric nervous system. Notably, Toll-like receptor 2 and Toll-like receptor 4 are dysregulated in Parkinson's disease patients and may therefore be identified as the core of early gut dysfunction in Parkinson's disease. To better understand the contribution of Toll-like receptor 2 and Toll-like receptor 4 dysfunction in the gut to early α-synuclein aggregation, we discussed the structural function of Toll-like receptor 2 and Toll-like receptor 4 and signal transduction of Toll-like receptor 2 and Toll-like receptor 4 in Parkinson's disease by reviewing clinical, animal models, and in vitro studies. We also present a conceptual model of the pathogenesis of Parkinson's disease, in which microbial dysbiosis alters the gut barrier as well as the Toll-like receptor 2 and Toll-like receptor 4 signaling pathways, ultimately leading to a positive feedback loop for chronic gut dysfunction, promoting α-synuclein aggregation in the gut and vagus nerve.

Enteric nervous system as a target and source of SARS-CoV-2 and other viral infections.

Coronavirus disease 2019 (COVID-19) has been demonstrated to affect several systems of the human body, including the gastrointestinal and nervous systems. The enteric nervous system (ENS) is a division of the autonomic nervous system that extends throughout the gut, regulates gastrointestinal function, and is therefore involved in most gut dysfunctions, including those resulting from many viral infections. Growing evidence highlights enteric neural cells and microbiota as important players in gut inflammation and dysfunction. Furthermore, the ENS and gastrointestinal immune system work together establishing relevant neuroimmune interactions during both health and disease. In recent years, gut-driven processes have also been implicated as players in systemic inflammation and in the initiation and propagation of several central nervous system pathologies, which seem to be hallmarks of COVID-19. In this review, we aim to describe evidence of the gastrointestinal and ENS infection with a focus on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We discuss here viral-induced mechanisms, neuroplasticity, and neuroinflammation to call attention to the enteric neuroglial network as a nervous system with a sensitive and crucial position to be not only a target of the new coronavirus but also a way in and trigger of COVID-19-related symptoms.

The Role of Probiotics and Their Metabolites in the Treatment of Depression.

Depression is a common and complex mental and emotional disorder that causes disability, morbidity, and quite often mortality around the world. Depression is closely related to several physical and metabolic conditions causing metabolic depression. Studies have indicated that there is a relationship between the intestinal microbiota and the brain, known as the gut-brain axis. While this microbiota-gut-brain connection is disturbed, dysfunctions of the brain, immune system, endocrine system, and gastrointestinal tract occur. Numerous studies show that intestinal dysbiosis characterized by abnormal microbiota and dysfunction of the microbiota-gut-brain axis could be a direct cause of mental and emotional disorders. Traditional treatment of depression includes psychotherapy and pharmacotherapy, and it mainly targets the brain. However, restoration of the intestinal microbiota and functions of the gut-brain axis via using probiotics, their metabolites, prebiotics, and healthy diet may alleviate depressive symptoms. Administration of probiotics labeled as psychobiotics and their metabolites as metabiotics, especially as an adjuvant to antidepressants, improves mental disorders. It is a new approach to the prevention, management, and treatment of mental and emotional illnesses, particularly major depressive disorder and metabolic depression. For the effectiveness of antidepressant therapy, psychobiotics should be administered at a dose higher than 1 billion CFU/day for at least 8 weeks.

Gut and airway microbiota dysbiosis and their role in COVID-19 and long-COVID.

The gut microbiota plays a crucial role in human health and disease. Gut dysbiosis is known to be associated with increased susceptibility to respiratory diseases and modifications in the immune response and homeostasis of the lungs (the so-called gut-lung axis). Furthermore, recent studies have highlighted the possible role of dysbiosis in neurological disturbances, introducing the notion of the "gut-brain axis." During the last 2 years, several studies have described the presence of gut dysbiosis during coronavirus disease 2019 (COVID-19) and its relationship with disease severity, SARS-CoV-2 gastrointestinal replication, and immune inflammation. Moreover, the possible persistence of gut dysbiosis after disease resolution may be linked to long-COVID syndrome and particularly to its neurological manifestations. We reviewed recent evidence on the association between dysbiosis and COVID-19, investigating the possible epidemiologic confounding factors like age, location, sex, sample size, the severity of disease, comorbidities, therapy, and vaccination status on gut and airway microbial dysbiosis in selected studies on both COVID-19 and long-COVID. Moreover, we analyzed the confounding factors strictly related to microbiota, specifically diet investigation and previous use of antibiotics/probiotics, and the methodology used to study the microbiota (α- and ß-diversity parameters and relative abundance tools). Of note, only a few studies focused on longitudinal analyses, especially for long-term observation in long-COVID. Lastly, there is a lack of knowledge regarding the role of microbiota transplantation and other therapeutic approaches and their possible impact on disease progression and severity. Preliminary data seem to suggest that gut and airway dysbiosis might play a role in COVID-19 and in long-COVID neurological symptoms. Indeed, the development and interpretation of these data could have important implications for future preventive and therapeutic strategies.

Anxiety level and functional dyspepsia incidence during COVID-19 pandemic

The adaptation process of the learning system, the hospital environment, and the high risk of COVID-19 infection can be stressors for anxiety in clinical clerkship. Through the brain-gut–axis, the interaction of psychological factors, such as anxiety, can trigger symptoms related to functional dyspepsia. This study aimed to determine the relationship between anxiety levels and functional dyspepsia during the COVID-19 pandemic among clinical clerkship students. This research was conducted on clinical clerkship students/young doctors in 2021. This was an observational analytic study with a cross-sectional approach and involved 131 respondents. The hamilton anxiety rating scale (HARS) questionnaire was utilized to quantify the level of anxiety, while functional dyspepsia was measured based on Rome IV criteria. The data were analyzed by the Lambda (λ) coefficient of correlation test. This study revealed a significant relationship between anxiety level and functional dyspepsia during the COVID-19 pandemic. © 2023, Intelektual Pustaka Media Utama. All rights reserved.

Effect of a Multi-Strain Probiotic Supplementation to Manage Stress during the COVID-19 Pandemic: A Randomized, Double-Blind, Placebo-Controlled, Cross-Over Clinical Trial.

INTRODUCTION: The COVID-19 pandemic strongly affected every aspect of the modern society, from health to socioeconomics, leading people to experience high levels of stress. METHODS: A double-blind, cross-over, placebo-controlled clinical study was performed to investigate the ability of a food supplement containing two probiotic strains, Limosilactobacillus reuteri PBS072 and Bifidobacterium breve BB077, in supporting 33 healthy adults, working at a university, in stress management. The efficacy of the tested strains in influencing the stress response, in terms of mood and sleep behavior, was assessed using the following validated questionnaires: Profile of Mood State (POMS) and Pittsburgh Sleep Quality Index (PSQI). RESULTS: Outcomes of the POMS and the PSQI demonstrated a significant reduction of the questionnaire's scores both versus baseline and placebo after 30 days of probiotic intake. CONCLUSIONS: According to the results, the probiotic food supplement investigated showed a remarkable effect on stress management by improving the quality of sleep and the mood.

The contribution of gut-brain axis to development of neurological symptoms in COVID-19 recovered patients: A hypothesis and review of literature.

The gut microbiota undergoes significant alterations in response to viral infections, particularly the novel SARS-CoV-2. As impaired gut microbiota can trigger numerous neurological disorders, we suggest that the long-term neurological symptoms of COVID-19 may be related to intestinal microbiota disorders in these patients. Thus, we have gathered available information on how the virus can affect the microbiota of gastrointestinal systems, both in the acute and the recovery phase of the disease, and described several mechanisms through which this gut dysbiosis can lead to long-term neurological disorders, such as Guillain-Barre syndrome, chronic fatigue, psychiatric disorders such as depression and anxiety, and even neurodegenerative diseases such as Alzheimer's and Parkinson's disease. These mechanisms may be mediated by inflammatory cytokines, as well as certain chemicals such as gastrointestinal hormones (e.g., CCK), neurotransmitters (e.g., 5-HT), etc. (e.g., short-chain fatty acids), and the autonomic nervous system. In addition to the direct influences of the virus, repurposed medications used for COVID-19 patients can also play a role in gut dysbiosis. In conclusion, although there are many dark spots in our current knowledge of the mechanism of COVID-19-related gut-brain axis disturbance, based on available evidence, we can hypothesize that these two phenomena are more than just a coincidence and highly recommend large-scale epidemiologic studies in the future.

Melatonin-Microbiome Two-Sided Interaction in Dysbiosis-Associated Conditions.

Melatonin is a pineal indolamine, allegedly known as a circadian rhythm regulator, and an antioxidative and immunomodulatory molecule. In both experimental and clinical trials, melatonin has been shown to have positive effects in various pathologies, as a modulator of important biochemical pathways including inflammation, oxidative stress, cell injury, apoptosis, and energy metabolism. The gut represents one of melatonin's most abundant extra pineal sources, with a 400-times-higher concentration than the pineal gland. The importance of the gut microbial community-namely, the gut microbiota, in multiple critical functions of the organism- has been extensively studied throughout time, and its imbalance has been associated with a variety of human pathologies. Recent studies highlight a possible gut microbiota-modulating role of melatonin, with possible implications for the treatment of these pathologies. Consequently, melatonin might prove to be a valuable and versatile therapeutic agent, as it is well known to elicit positive functions on the microbiota in many dysbiosis-associated conditions, such as inflammatory bowel disease, chronodisruption-induced dysbiosis, obesity, and neuropsychiatric disorders. This review intends to lay the basis for a deeper comprehension of melatonin, gut microbiota, and host-health subtle interactions.

The PROVIT Study-Effects of Multispecies Probiotic Add-on Treatment on Metabolomics in Major Depressive Disorder-A Randomized, Placebo-Controlled Trial.

The gut-brain axis plays a role in major depressive disorder (MDD). Gut-bacterial metabolites are suspected to reduce low-grade inflammation and influence brain function. Nevertheless, randomized, placebo-controlled probiotic intervention studies investigating metabolomic changes in patients with MDD are scarce. The PROVIT study (registered at clinicaltrials.com NCT03300440) aims to close this scientific gap. PROVIT was conducted as a randomized, single-center, double-blind, placebo-controlled multispecies probiotic intervention study in individuals with MDD (n = 57). In addition to clinical assessments, metabolomics analyses (1H Nuclear Magnetic Resonance Spectroscopy) of stool and serum, and microbiome analyses (16S rRNA sequencing) were performed. After 4 weeks of probiotic add-on therapy, no significant changes in serum samples were observed, whereas the probiotic groups' (n = 28) stool metabolome shifted towards significantly higher concentrations of butyrate, alanine, valine, isoleucine, sarcosine, methylamine, and lysine. Gallic acid was significantly decreased in the probiotic group. In contrast, and as expected, no significant changes resulted in the stool metabolome of the placebo group. Strong correlations between bacterial species and significantly altered stool metabolites were obtained. In summary, the treatment with multispecies probiotics affects the stool metabolomic profile in patients with MDD, which sets the foundation for further elucidation of the mechanistic impact of probiotics on depression.

Mental Health Symptom Reduction Using Digital Therapeutics Care Informed by Genomic SNPs and Gut Microbiome Signatures.

Neuropsychiatric diseases and obesity are major components of morbidity and health care costs, with genetic, lifestyle, and gut microbiome factors linked to their etiology. Dietary and weight-loss interventions can help improve mental health, but there is conflicting evidence regarding their efficacy; and moreover, there is substantial interindividual heterogeneity that needs to be understood. We aimed to identify genetic and gut microbiome factors that explain interindividual differences in mental health improvement after a dietary and lifestyle intervention for weight loss. We recruited 369 individuals participating in Digbi Health's personalized digital therapeutics care program and evaluated the association of 23 genetic scores, the abundance of 178 gut microbial genera, and 42 bacterial pathways with mental health. We studied the presence/absence of anxiety or depression, or sleep problems at baseline and improvement on anxiety, depression, and insomnia after losing at least 2% body weight. Participants lost on average 5.4% body weight and >95% reported improving mental health symptom intensity. There were statistically significant correlations between: (a) genetic scores with anxiety or depression at baseline, gut microbial functions with sleep problems at baseline, and (b) genetic scores and gut microbial taxa and functions with anxiety, depression, and insomnia improvement. Our results are concordant with previous findings, including the association between anxiety or depression at baseline with genetic scores for alcohol use disorder and major depressive disorder. As well, our results uncovered new associations in line with previous epidemiological literature. As evident from previous literature, we also observed associations of gut microbial signatures with mental health including short-chain fatty acids and bacterial neurotoxic metabolites specifically with depression. Our results also show that microbiome and genetic factors explain self-reported mental health status and improvement better than demographic variables independently. The genetic and microbiome factors identified in this study provide the basis for designing and personalizing dietary interventions to improve mental health.

Effects of Two Distinct Psychoactive Microbes, Lacticaseibacillus rhamnosus JB-1 and Limosilactobacillus reuteri 6475, on Circulating and Hippocampal mRNA in Male Mice.

Discovery of the microbiota-gut-brain axis has led to proposed microbe-based therapeutic strategies in mental health, including the use of mood-altering bacterial species, termed psychobiotics. However, we still have limited understanding of the key signaling pathways engaged by specific organisms in modulating brain function, and evidence suggests that bacteria with broadly similar neuroactive and immunomodulatory actions can drive different behavioral outcomes. We sought to identify pathways distinguishing two psychoactive bacterial strains that seemingly engage similar gut-brain signaling pathways but have distinct effects on behaviour. We used RNAseq to identify mRNAs differentially expressed in the blood and hippocampus of mice following Lacticaseibacillus rhamnosus JB-1, and Limosilactobacillus reuteri 6475 treatment and performed Gene Set Enrichment Analysis (GSEA) to identify enrichment in pathway activity. L. rhamnosus, but not L. reuteri treatment altered several pathways in the blood and hippocampus, and the rhamnosus could be clearly distinguished based on mRNA profile. In particular, L. rhamnosus treatment modulated the activity of interferon signaling, JAK/STAT, and TNF-alpha via NF-KB pathways. Our results highlight that psychobiotics can induce complex changes in host gene expression, andin understanding these changes, we may help fine-tune selection of psychobiotics for treating mood disorders.

Gut-brain communication in COVID-19: molecular mechanisms, mediators, biomarkers, and therapeutics.

INTRODUCTION: Infection with COVID-19 results in acute respiratory symptoms followed by long COVID multi-organ effects presenting with neurological, cardiovascular, musculoskeletal, and gastrointestinal (GI) manifestations. Temporal relationship between gastrointestinal and neurological symptoms is unclear but warranted for exploring better clinical care for COVID-19 patients. AREAS COVERED: We critically reviewed the temporal relationship between gut-brain axis after SARS-CoV-2 infection and the molecular mechanisms involved in neuroinvasion following GI infection. Mediators are identified that could serve as biomarkers and therapeutic targets in SARS-CoV-2. We discussed the potential therapeutic approaches to mitigate the effects of GI infection with SARS-CoV-2. EXPERT OPINION: Altered gut microbiota cause increased expression of various mediators, including zonulin causing disruption of tight junction. This stimulates enteric nervous system and signals to CNS precipitating neurological sequalae. Published reports suggest potential role of cytokines, immune cells, B(0)AT1 (SLC6A19), ACE2, TMRSS2, TMPRSS4, IFN-γ, IL-17A, zonulin, and altered gut microbiome in gut-brain axis and associated neurological sequalae. Targeting these mediators and gut microbiome to improve immunity will be of therapeutic significance. In-depth research and well-designed large-scale population-based clinical trials with multidisciplinary and collaborative approaches are warranted. Investigating the temporal relationship between organs involved in long-term sequalae is critical due to evolving variants of SARS-CoV-2.

Perspective: Chicken Models for Studying the Ontogenetic Origin of Neuropsychiatric Disorders.

Nutrients and xenobiotics cross the blood-placenta barrier, potentially depositing in the fetal brain. The prenatal exposure affects the neuroendocrine and microbial development. The mechanism underlying maternal risk factors reprograming the microbiota-gut-brain axis with long-term effects on psychosocial behaviors in offspring is not clear. In humans, it is not possible to assess the nutrient or xenobiotic deposition in the fetal brain and gastrointestinal system for ethical reasons. Moreover, the maternal-fetal microbe transfer during gestation, natural labor, and breast-feeding constitutes the initial gut microbiome in the progeny, which is inevitable in the most widely utilized rodent models. The social predisposition in precocial birds, including chickens, provides the possibility to test behavioral responses shortly after being hatched. Hence, chickens are advantageous in investigating the ontogenetic origin of behaviors. Chicken embryos are suitable for deposition assessment and mechanistic study due to the accessibility, self-contained development, uniform genetic background, robust microbiota, and easy in vivo experimental manipulation compared to humans and rodents. Therefore, chicken embryos can be used as an alternative to the rodent models in assessing the fetal exposure effect on neurogenesis and investigating the mechanism underlying the ontogenetic origin of neuropsychiatric disorders.

Shedding light on biological sex differences and microbiota-gut-brain axis: a comprehensive review of its roles in neuropsychiatric disorders.

Women and men are suggested to have differences in vulnerability to neuropsychiatric disorders, including major depressive disorder (MDD), generalized anxiety disorder (GAD), schizophrenia, eating disorders, including anorexia nervosa, and bulimia nervosa, neurodevelopmental disorders, such as autism spectrum disorder (ASD), and neurodegenerative disorders including Alzheimer's disease, Parkinson's disease. Genetic factors and sex hormones are apparently the main mediators of these differences. Recent evidence uncovers that reciprocal interactions between sex-related features (e.g., sex hormones and sex differences in the brain) and gut microbiota could play a role in the development of neuropsychiatric disorders via influencing the gut-brain axis. It is increasingly evident that sex-microbiota-brain interactions take part in the occurrence of neurologic and psychiatric disorders. Accordingly, integrating the existing evidence might help to enlighten the fundamental roles of these interactions in the pathogenesis of neuropsychiatric disorders. In addition, an increased understanding of the biological sex differences on the microbiota-brain may lead to advances in the treatment of neuropsychiatric disorders and increase the potential for precision medicine. This review discusses the effects of sex differences on the brain and gut microbiota and the putative underlying mechanisms of action. Additionally, we discuss the consequences of interactions between sex differences and gut microbiota on the emergence of particular neuropsychiatric disorders.

Voluntary Wheel Running in Old C57BL/6 Mice Reduces Age-Related Inflammation in the Colon but Not in the Brain.

Inflammation is considered a possible cause of cognitive decline during aging. This study investigates the influence of physical activity and social isolation in old mice on their cognitive functions and inflammation. The Barnes maze task was performed to assess spatial learning and memory in 3, 9, 15, 24, and 28 months old male C57BL/6 mice as well as following voluntary wheel running (VWR) and social isolation (SI) in 20 months old mice. Inflammatory gene expression was analyzed in hippocampal and colonic samples by qPCR. Cognitive decline occurs in mice between 15 and 24 months of age. VWR improved cognitive functions while SI had negative effects. Expression of inflammatory markers changed during aging in the hippocampus (Il1a/Il6/S100b/Iba1/Adgre1/Cd68/Itgam) and colon (Tnf/Il6/Il1ra/P2rx7). VWR attenuates inflammaging specifically in the colon (Ifng/Il10/Ccl2/S100b/Iba1), while SI regulates intestinal Il1b and Gfap. Inflammatory markers in the hippocampus were not altered following VWR and SI. The main finding of our study is that both the hippocampus and colon exhibit an increase in inflammatory markers during aging, and that voluntary wheel running in old age exclusively attenuates intestinal inflammation. Based on the existence of the gut-brain axis, our results extend therapeutic approaches preserving cognitive functions in the elderly to the colon.

Microbes and Parkinson's disease: from associations to mechanisms.

Parkinson's disease (PD) is a neurodegenerative disorder influenced by both genetic and environmental factors. The mechanisms leading to neurodegeneration in PD are still under investigation, with several mechanistic models currently proposed. A number of microorganisms have been associated with increased risk of PD in humans, and recent research using newly developed models has begun to elucidate how these microbes may factor into disease development. Newly identified roles for PD-associated genes in host-microbe interactions and response to infections have also recently been uncovered, providing further evidence for microbial contributions to PD. Here we summarize these recent advances in the field and discuss them in the context of both historical and emerging hypotheses for PD development, with a particular focus on the application of rodent models as systems allowing for mechanistic hypothesis testing.

Gut Microbiota Metabolites in Major Depressive Disorder-Deep Insights into Their Pathophysiological Role and Potential Translational Applications.

The gut microbiota is a complex and dynamic ecosystem essential for the proper functioning of the organism, affecting the health and disease status of the individuals. There is continuous and bidirectional communication between gut microbiota and the host, conforming to a unique entity known as "holobiont". Among these crosstalk mechanisms, the gut microbiota synthesizes a broad spectrum of bioactive compounds or metabolites which exert pleiotropic effects on the human organism. Many of these microbial metabolites can cross the blood-brain barrier (BBB) or have significant effects on the brain, playing a key role in the so-called microbiota-gut-brain axis. An altered microbiota-gut-brain (MGB) axis is a major characteristic of many neuropsychiatric disorders, including major depressive disorder (MDD). Significative differences between gut eubiosis and dysbiosis in mental disorders like MDD with their different metabolite composition and concentrations are being discussed. In the present review, the main microbial metabolites (short-chain fatty acids -SCFAs-, bile acids, amino acids, tryptophan -trp- derivatives, and more), their signaling pathways and functions will be summarized to explain part of MDD pathophysiology. Conclusions from promising translational approaches related to microbial metabolome will be addressed in more depth to discuss their possible clinical value in the management of MDD patients.

Post-infection functional gastrointestinal disorders following coronavirus disease-19: A case-control study.

BACKGROUND AND AIM: Because acute infectious gastroenteritis may cause post-infection irritable bowel syndrome and functional dyspepsia and the severe acute respiratory syndrome coronavirus-2 affects gastrointestinal (GI) tract, coronavirus disease-19 (COVID-19) may cause post-infection-functional GI disorders (FGIDs). We prospectively studied the frequency and spectrum of post-infection-FGIDs among COVID-19 and historical healthy controls and the risk factors for its development. METHODS: Two hundred eighty patients with COVID-19 and 264 historical healthy controls were followed up at 1 and 3 months using translated validated Rome Questionnaires for the development of chronic bowel dysfunction (CBD), dyspeptic symptoms, and their overlap and at 6-month for IBS, uninvestigated dyspepsia (UD) and their overlap. Psychological comorbidity was studied using Rome III Psychosocial Alarm Questionnaire. RESULTS: At 1 and 3 months, 16 (5.7%), 16 (5.7%), 11 (3.9%), and 24 (8.6%), 6 (2.1%), 9 (3.2%) of COVID-19 patients developed CBD, dyspeptic symptoms, and their overlap, respectively; among healthy controls, none developed dyspeptic symptoms and one developed CBD at 3 months (P < 0.05). At 6 months, 15 (5.3%), 6 (2.1%), and 5 (1.8%) of the 280 COVID-19 patients developed IBS, UD, and IBS-UD overlap, respectively, and one healthy control developed IBS at 6 months (P < 0.05 for all except IBS-UD overlap). The risk factors for post-COVID-19 FGIDs at 6 months included symptoms (particularly GI), anosmia, ageusia, and presence of CBD, dyspeptic symptoms, or their overlap at 1 and 3 months and the psychological comorbidity. CONCLUSIONS: This is the first study showing COVID-19 led to post-COVID-19 FGIDs. Post-COVID-19 FGIDs may pose a significant economic, social, and healthcare burden to the world.

COVID-19 as a trigger of irritable bowel syndrome: A review of potential mechanisms.

In December 2019 a novel coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), started spreading from Wuhan city of Chinese Hubei province and rapidly became a global pandemic. Clinical symptoms of the disease range from paucisymptomatic disease to a much more severe disease. Typical symptoms of the initial phase include fever and cough, with possible progression to acute respiratory distress syndrome. Gastrointestinal manifestations such as diarrhoea, vomiting and abdominal pain are reported in a considerable number of affected individuals and may be due to the SARS-CoV-2 tropism for the peptidase angiotensin receptor 2. The intestinal homeostasis and microenvironment appear to play a major role in the pathogenesis of COVID-19 and in the enhancement of the systemic inflammatory responses. Long-term consequences of COVID-19 include respiratory disturbances and other disabling manifestations, such as fatigue and psychological impairment. To date, there is a paucity of data on the gastrointestinal sequelae of SARS-CoV-2 infection. Since COVID-19 can directly or indirectly affect the gut physiology in different ways, it is plausible that functional bowel diseases may occur after the recovery because of potential pathophysiological alterations (dysbiosis, disruption of the intestinal barrier, mucosal microinflammation, post-infectious states, immune dysregulation and psychological stress). In this review we speculate that COVID-19 can trigger irritable bowel syndrome and we discuss the potential mechanisms.