Bacterial DnaK reduces the activity of anti-cancer drugs cisplatin and 5FU.

BACKGROUND: Chemotherapy is a primary treatment for cancer, but its efficacy is often limited by cancer-associated bacteria (CAB) that impair tumor suppressor functions. Our previous research found that Mycoplasma fermentans DnaK, a chaperone protein, impairs p53 activities, which are essential for most anti-cancer chemotherapeutic responses. METHODS: To investigate the role of DnaK in chemotherapy, we treated cancer cell lines with M. fermentans DnaK and then with commonly used p53-dependent anti-cancer drugs (cisplatin and 5FU). We evaluated the cells' survival in the presence or absence of a DnaK-binding peptide (ARV-1502). We also validated our findings using primary tumor cells from a novel DnaK knock-in mouse model. To provide a broader context for the clinical significance of these findings, we investigated human primary cancer sequencing datasets from The Cancer Genome Atlas (TCGA). We identified F. nucleatum as a CAB carrying DnaK with an amino acid composition highly similar to M. fermentans DnaK. Therefore, we investigated the effect of F. nucleatum DnaK on the anti-cancer activity of cisplatin and 5FU. RESULTS: Our results show that both M. fermentans and F. nucleatum DnaKs reduce the effectiveness of cisplatin and 5FU. However, the use of ARV-1502 effectively restored the drugs' anti-cancer efficacy. CONCLUSIONS: Our findings offer a practical framework for designing and implementing novel personalized anti-cancer strategies by targeting specific bacterial DnaKs in patients with poor response to chemotherapy, underscoring the potential for microbiome-based personalized cancer therapies.

Mycoplasma DnaK expression increases cancer development in vivo upon DNA damage.

Well-controlled repair mechanisms are involved in the maintenance of genomic stability, and their failure can precipitate DNA abnormalities and elevate tumor risk. In addition, the tumor microenvironment, enriched with factors inducing oxidative stress and affecting cell cycle checkpoints, intensifies DNA damage when repair pathways falter. Recent research has unveiled associations between certain bacteria, including Mycoplasmas, and various cancers, and the causative mechanism(s) are under active investigation. We previously showed that Mycoplasma fermentans DnaK, an HSP70 family chaperone protein, hampers the activity of proteins like PARP1 and p53, crucial for genomic integrity. Moreover, our analysis of its interactome in human cancer cell lines revealed DnaK's engagement with several components of DNA-repair machinery. Finally, in vivo experiments performed in our laboratory using a DnaK knock-in mouse model generated by our group demonstrated that DnaK exposure led to increased DNA copy number variants, indicative of genomic instability. We present here evidence that expression of DnaK is linked to increased i) incidence of tumors in vivo upon exposure to urethane, a DNA damaging agent; ii) spontaneous DNA damage ex vivo; and iii) expression of proinflammatory cytokines ex vivo, variations in reactive oxygen species levels, and increased ß-galactosidase activity across tissues. Moreover, DnaK was associated with increased centromeric instability. Overall, these findings highlight the significance of Mycoplasma DnaK in the etiology of cancer and other genetic disorders providing a promising target for prevention, diagnostics, and therapeutics.

Measuring the neglected anxiety disorder: validation of the social anxiety spectrum-short version (SHY-SV) questionnaire.

BACKGROUND: In the recent years, a growing body of literature stressed the importance of a dimensional perspective on mental disorders. In particular, since its conceptualization, one of the main concerns in the field of Social Anxiety Disorder (SAD) has been the definition of a diagnostic threshold, leading to the suggestion that SAD may be more properly classified as a spectrum of severity rather than a discrete disorder based on subjectively determined threshold. The purpose of the current research is to evaluate the psychometric qualities of the Social Anxiety Spectrum - Short Version (SHY-SV), a novel questionnaire designed to measure the complete range of social anxiety symptoms, from overt manifestations to subthreshold ones. METHODS: 42 subjects with a clinical diagnosis of social anxiety disorder (SAD) according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), 43 subjects with a clinical diagnosis of Obsessive-Compulsive Disorder (OCD) and 60 individuals without current or lifetime mental disorders (HC) were recruited from the Psychiatric Clinic of the University of Pisa. Subjects were assessed with the SCID-5, Liebowitz Social Anxiety Scale (LSAS) and the SHY-SV. RESULTS: SHY-SV showed strong internal consistency, and both the total and domain scores had great test-retest reliability. The Pearson's coefficients for the SHY-SV domain scores ranged from 0.391 to 0.933, and they were positively and significantly correlated with one another (p 0.001). All the SHY-SV domain scores were highly correlated with the SHY-SV total score. Results from of the correlation coefficients between SHY-SV and alternative measures of SAD were all significant and positive. Significant differences among diagnostic groups on both SAD-SV domains and total scores were found. SAD-SV total score increased significantly and progressively from HCs, to the OCD up to the SAD group which showed the highest values. CONCLUSION: The SHY-SV demonstrated significant convergent validity with other dimensional SAD measures, great internal consistency, and test-retest reliability. With an increasing score gradient from healthy controls to patients with OCD to those with SAD, the questionnaire performed differently in each of the three diagnostic categories.

Joining Forces against Antibiotic Resistance: The One Health Solution.

Antibiotic resistance is a significant global health concern that affects both human and animal populations. The One Health approach acknowledges the interconnectedness of human health, animal health, and the environment. It emphasizes the importance of collaboration and coordination across these sectors to tackle complex health challenges such as antibiotic resistance. In the context of One Health, antibiotic resistance refers to the ability of bacteria to withstand the efficacy of antibiotics, rendering them less effective or completely ineffective in treating infections. The emergence and spread of antibiotic-resistant bacteria pose a threat to human and animal health, as well as to the effectiveness of medical treatments and veterinary interventions. In particular, One Health recognizes that antibiotic use in human medicine, animal agriculture, and the environment are interconnected factors contributing to the development and spread of antibiotic resistance. For example, the misuse and overuse of antibiotics in human healthcare, including inappropriate prescribing and patient non-compliance, can contribute to the selection and spread of resistant bacteria. Similarly, the use of antibiotics in livestock production for growth promotion and disease prevention can contribute to the development of antibiotic resistance in animals and subsequent transmission to humans through the food chain. Addressing antibiotic resistance requires a collaborative One Health approach that involves multiple participants, including healthcare professionals, veterinarians, researchers, and policymakers.

Monitoring Monkeypox: Safeguarding Global Health through Rapid Response and Global Surveillance.

Monkeypox, a viral zoonotic disease, has emerged as a significant global threat in recent years. This review focuses on the importance of global monitoring and rapid response to monkeypox outbreaks. The unpredictable nature of monkeypox transmissions, its potential for human-to-human spread, and its high morbidity rate underscore the necessity for proactive surveillance systems. By analyzing the existing literature, including recent outbreaks, this review highlights the critical role of global surveillance in detecting, containing, and preventing the further spread of monkeypox. It also emphasizes the need for enhanced international collaboration, data sharing, and real-time information exchange to effectively respond to monkeypox outbreaks as a global health concern. Furthermore, this review discusses the challenges and opportunities of implementing robust surveillance strategies, including the use of advanced diagnostic tools and technologies. Ultimately, these findings underscore the urgency of establishing a comprehensive global monitoring framework for monkeypox, enabling early detection, prompt response, and effective control measures to protect public health worldwide.

Autistic and Catatonic Spectrum Symptoms in Patients with Borderline Personality Disorder.

BACKGROUND: Recent literature has shown that a considerable percentage of patients with severe mental disorders can develop, over time, full-blown or subthreshold catatonia. Some studies corroborate the model of an illness trajectory in which different mental disorders would be arranged along a continuum of severity until the development of catatonia. In such an illness pathway, autistic traits (AT) and borderline personality disorder (BPD) may represent important steps. In order to further explore the association between AT, BPD, and catatonia, the aim of this study was to compare catatonic spectrum symptoms and AT among patients with major depressive disorder (MDD), BPD, and healthy controls (CTL), also evaluating possible predictive dimensions of the different diagnoses. METHODS: A total of 90 adults affected by BPD, 90 adults with a diagnosis of MDD, and 90 CTL, homogeneous in terms of gender and age, were recruited from six Italian university departments of psychiatry and assessed with the SCID-5-RV, the Catatonia Spectrum (CS), and the Adult Autism Subthreshold Autism Spectrum (AdAS Spectrum). RESULTS: The total CS score was significantly higher in the BPD and MDD groups than in the CTL group, while the majority of CS domain scores were significantly higher in the BPD group than in the MDD group, which scored significantly higher than the CTL group. The total AdAS Spectrum score and the AdAS Spectrum domain scores were significantly higher in the BPD group than in the MDD group, which in turn scored significantly higher than the CTL group. The CS domains "psychomotor activity" and "impulsivity", and AdAS Spectrum domains "verbal communication", "empathy", and "hyper-/hyporeactivity to sensory input" were associated with the risk of presenting a diagnosis of BPD.

Update on the Phylodynamic and Genetic Variability of Marburg Virus.

The COVID-19 pandemic has not only strained healthcare systems in Africa but has also intensified the impact of emerging and re-emerging diseases. Specifically in Equatorial Guinea, mirroring the situation in other African countries, unique zoonotic outbreaks have occurred during this challenging period. One notable resurgence is Marburg virus disease (MVD), which has further burdened the already fragile healthcare system. The re-emergence of the Marburg virus amid the COVID-19 pandemic is believed to stem from a probable zoonotic spill-over, although the precise transmission routes remain uncertain. Given the gravity of the situation, addressing the existing challenges is paramount. Though the genome sequences from the current outbreak were not available for this study, we analyzed all the available whole genome sequences of this re-emerging pathogen to advocate for a shift towards active surveillance. This is essential to ensure the successful containment of any potential Marburg virus outbreak in Equatorial Guinea and the wider African context. This study, which presents an update on the phylodynamics and the genetic variability of MARV, further confirmed the existence of at least two distinct patterns of viral spread. One pattern demonstrates a slower but continuous and recurring virus circulation, while the other exhibits a faster yet limited and episodic spread. These results highlight the critical need to strengthen genomic surveillance in the region to effectively curb the pathogen's dissemination. Moreover, the study emphasizes the importance of prompt alert management, comprehensive case investigation and analysis, contact tracing, and active case searching. These steps are vital to support the healthcare system's response to this emerging health crisis. By implementing these strategies, we can better arm ourselves against the challenges posed by the resurgence of the Marburg virus and other infectious diseases.

The mediating effect of mood spectrum on the relationship between autistic traits and catatonia spectrum.

Background: In the recent years, several studies have shown a correlation between autism spectrum disorder (ASD) and catatonia. It is also known that both conditions are found to be associated with mood disorders. This study aimed to investigate the relationship between autistic traits and catatonic symptoms, as well as the potential mediating role of mood disorder spectrum in the relationship between them. Methods: The total sample of 514 subjects was composed by four diagnostic groups, composed by patients affected by catatonia (CTN), borderline personality disorder (BPD), major depressive disorder (MDD) and healthy controls (HC). Subjects were assessed with the SCID-5-RV, the Adult Autism Subthreshold Spectrum (AdAS Spectrum) and the Catatonia Spectrum (CS) and the Mood Spectrum Self-Report (MOODS-SR). Statistical analyses included Pearson's coefficient calculation, multiple linear regression, and mediation analysis. Results: all the correlations appear to be strongly positive and significant with the strongest coefficient emerging between AdAS Spectrum total score and CS total score (r = 0.762, p < 0.001). The Mediation Analysis showed that AdAS Spectrum total score showed a significant indirect effect on CS total score through MOODS-SR total score (b = 0.168, 95% bootstrapped CI [0.127:0.207]). Conclusion: The present study highlights the presence of a mediating role of the mood disorder spectrum in the relationship between autistic traits and the catatonia spectrum.

Validation of the short version of the obsessive compulsive spectrum questionnaire.

Aim: In the recent years, a rising amount of research has stressed the importance of a dimensional perspective on mental disorders. In particular, the conceptualization of an obsessive-compulsive spectrum appears to be in line with the very first descriptions of Obsessive-Compulsive Disorder and has been partially acknowledged by the inclusion of the "OCD-spectrum related syndromes and disorders" section in the DSM-5. The goal of the current study is to ascertain the psychometric characteristics of the Obsessive-Compulsive Spectrum-Short Version (OBS-SV), a novel questionnaire designed to measure the complete range of obsessive-compulsive symptoms, from severe full blown to subthreshold ones. Methods: Forty three subjects with a clinical diagnosis of OCD according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-5); 42 subjects with a clinical diagnosis of social anxiety disorder (SAD), and 60 individuals without current or lifetime mental disorders (HC) were recruited from the Psychiatric Clinic of the University of Pisa. Subjects were assessed with the SCID-5, the Yale Brown Obsessive Compulsive Scale (Y-BOCS) and the OBS-SV. Results: OBS-SV showed strong test-retest reliability for both the total and the domains scores, as well as a high level of internal consistency. The Pearson's coefficients for the OBS-SV domain scores ranged from 0.771 to 0.943, and they were positively and strongly linked with one another (p < 0.001). The OBS-SV total score had a strong correlation with each of the OBS-SV domain scores. All correlation coefficients between OBS-SV and additional measures of OCS were observed to be strong, significant and positive. Both OBS-SV domain and overall score differences between diagnostic groups were found to be statistically significant. From HCs, to the SAD, up to the OC group, which had the highest values, the OBS-SV total score grew dramatically and progressively. Conclusion: The OBS-SV demonstrated significant convergent validity with other dimensional OCD measures, excellent internal consistency, and test-retest reliability. Across the three diagnostic categories, the questionnaire functioned differently, with a rising score gradient from healthy controls through SAD patients to OCD subjects.

Mycoplasma DnaK increases DNA copy number variants in vivo.

The human microbiota affects critical cellular functions, although the responsible mechanism(s) is still poorly understood. In this regard, we previously showed that Mycoplasma fermentans DnaK, an HSP70 chaperone protein, hampers the activity of important cellular proteins responsible for DNA integrity. Here, we describe a novel DnaK knock-in mouse model generated in our laboratory to study the effect of M. fermentans DnaK expression in vivo. By using an array-based comparative genomic hybridization assay, we demonstrate that exposure to DnaK was associated with a higher number of DNA copy number variants (CNVs) indicative of unbalanced chromosomal alterations, together with reduced fertility and a high rate of fetal abnormalities. Consistent with their implication in genetic disorders, one of these CNVs caused a homozygous Grid2 deletion, resulting in an aberrant ataxic phenotype that recapitulates the extensive biallelic deletion in the Grid2 gene classified in humans as autosomal recessive spinocerebellar ataxia 18. Our data highlight a connection between components of the human urogenital tract microbiota, namely Mycoplasmas, and genetic abnormalities in the form of DNA CNVs, with obvious relevant medical, diagnostic, and therapeutic implications.

Investigating suicidality across the autistic-catatonic continuum in a clinical sample of subjects with major depressive disorder and borderline personality disorder.

Background: Recent literature has highlighted that catatonia may be more prevalent among psychiatric patients than previously thought, beginning from autism spectrum disorders (ASD), for which it has been suggested to represent a severe late consequence, but also among individuals with mood disorders and borderline personality disorder (BPD). Interestingly, one critical point shared by these conditions is the increased risk of suicidality. The aim of this study was to evaluate how the presence and the prevalence of catatonic symptoms may shape and correlate with suicidal risk in a sample of individuals with major depressive disorder (MDD) or BPD. Methods: We recruited two clinical samples of subjects (BPD and MDD) and a control group without a diagnosis according to DSM-5 (CTL). Subjects were assessed with the catatonia spectrum (CS) and the MOODS-SR for evaluating suicidality. Results: In the total sample, suicidality score was significantly and positively correlated with all CS domains and CS total score. Correlation and regression analyses highlighted specific patterns of association among Catatonia spectrum domains and suicidality in the MDD and BPD group and in the total sample. Conclusion: In both disorders, higher catatonic traits are linked to higher suicidal tendencies, confirming the high risk of suicide for this population. However, different patterns of association between catatonic symptoms and suicidality were highlighted in the two disorders.

Autistic traits distribution in different psychiatric conditions: A cluster analysis on the basis of the Adult Autism Subthreshold Spectrum (AdAS Spectrum) questionnaire.

Increasing interest is being paid on full-threshold and sub-threshold autism spectrum conditions among adults. Sub-threshold autistic traits (AT) seem to be distributed in a continuum from the clinical to the general population, being particularly higher among subjects with other psychiatric disorders. The aim of the present study was to evaluate the distribution of AT in a sample of subjects with different psychiatric conditions by means of a cluster analysis on the basis of the score reported to the AdAS Spectrum instrument. A total of 738 subjects recruited by seven Italian Universities were divided in 5 groups depending on the clinical diagnosis: Autism spectrum disorder (ASD), subthreshold ASD symptoms (partial ASD), Bipolar disorder (BD), Feeding and eating disorders (FED), and controls (CTLs). All subjects were assessed with the AdAS Spectrum. The cluster analysis identified 3 clusters: the high, medium and low autism clusters. The Restricted interests and rumination domain reported the highest influence in forming the clusters. The high, medium and low autism clusters were respectively more represented in the ASD, partial ASD and CTL groups. The clusters were represented intermediately in the FED and BD groups, confirming the presence of intermediate levels of AT in these clinical populations.

Validation of the Short Version of the Panic Agoraphobic Spectrum (PAS-SV) Questionnaire.

Objective: a spectrum model of psychopathology has allowed, in recent years, to recognize the subclinical or sub-threshold symptomatology that may be associated with full-blown mental disorders. The conceptualization of a panic - agoraphobic spectrum was developed in consideration of the substantial clinical heterogeneity revealed by studies on panic disorder with or without agoraphobia. The current study aims to determine the psychometric properties of the Panic Agoraphobic Spectrum - Short Version (PAS-SV), a new questionnaire designed to identify the spectrum of panic - agoraphobic symptoms. Method: 42 subjects with panic disorder or agoraphobia (PAD) according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), 41 subjects with autism spectrum disorder (ASD), and 60 healthy controls (HC) were recruited from the Psychiatric Clinic of the University of Pisa and assessed with the SCID-5, the Panic Disorder Severity Scale (PDSS) and the PAS-SV. Results: PAS-SV demonstrated a high level of internal consistency and the test-retest reliability for total and domain scores was excellent. PAS-SV domain scores were positively and significantly correlated with each other (p < 0.001), with Pearson's coefficients ranging from 0.771 to 0.943. All the PAS-SV domain scores were highly correlated with the PAS-SV total score. The correlation coefficients between PAS-SV and alternative measures of panic - agoraphobic symptoms appeared all significant and positive. Significant differences among diagnostic groups on both PAS-SV domains and total scores were found. PAS-SV total score increased significantly and progressively from HC, to the ASD up to the PA group. Conclusions: The PAS-SV showed excellent internal consistency and test-retest reliability and strong convergent validity with alternative dimensional measures of PA. The questionnaire performed differently among the three diagnostic groups, with an increasing score gradient from HC to patients with ASD to the PA group.

Neuroprotective properties of antiepileptics: what are the implications for psychiatric disorders?

Since the discovery of the first antiepileptic compound, increasing attention has been paid to antiepileptic drugs (AEDs), and recently, with the understanding of the molecular mechanism underlying cells death, a new interest has revolved around a potential neuroprotective effect of AEDs. While many neurobiological studies in this field have focused on the protection of neurons, growing data are reporting how exposure to AEDs can also affect glial cells and the plastic response underlying recovery; however, demonstrating the neuroprotective abilities of AEDs remains a changeling task. The present work aims to summarize and review the literature available on the neuroprotective properties of the most commonly used AEDs. Results highlighted how further studies should investigate the link between AEDs and neuroprotective properties; while many studies are available on valproate, results for other AEDs are very limited and the majority of the research has been carried out on animal models. Moreover, a better understanding of the biological basis underlying neuro-regenerative defects may pave the way for the investigation of further therapeutic targets and eventually lead to an improvement in the actual treatment strategies.

Occurrence of Terrifying Nightmares after Few Days of Mirtazapine Use in Elderly Patients.

Introduction. Sleep disturbance and insomnia are some of the most frequent complaints in patients suffering from depression. Some common antidepressant with excitatory effects may worsen sleep qualities, whereas others (like mirtazapine), thanks to their antihistaminergic action, are associated with sedative properties and can quickly improve sleep quality. In the case of mirtazapine, even if its mechanisms of action on sleep remain controversial, beneficial changes in sleep pattern may be observable since the first dose and are associated with a faster onset of the antidepressive action. Case Presentation. Despite these documented beneficial effects, we reported five cases of elderly patients (age ranging from 69 to 79) with various diagnoses and comorbidities (severe or recurrent depression, general anxiety disorder, borderline personality disorder, and Parkinson's disease) assessed during clinical daily routine for whom the use of mirtazapine was linked to the onset of nightmares so impressive and dramatic that made it necessary to interrupt the treatment. Discussion. This peculiar side effect is still scarcely documented, and the literature on this topic remains conflicting; however, considering that the cases were collected in a short range of time, the exacerbation of nightmares caused by mirtazapine may be more frequent than previously believed. Furthermore, some common features shared by all the cases reported have been highlighted such as the onset of the nightmares being chronologically associated with the initiation of the therapy with mirtazapine, the disappearance with the interruption, the similar age range of all, and the occurrence of the episodes described during fall season.

Orthorexia and autism spectrum in University workers: relationship with gender, body mass index and dietary habits.

OBJECTIVE: To date, few studies have investigated the relationship between autistic traits and emerging phenotypes of restrictive disorders, such as Orthorexia nervosa (ON). The aim of the present work was to investigate the relationship between ON symptoms and autistic traits in a population of University employees, focusing on the impact of gender, weight and type of diet. METHODS: All academic and technical/administrative workers of University of Pisa were invited by mail to fulfil through an anonymous online form the Adult Autism Sub-threshold Spectrum (AdAS Spectrum) and the ORTO-R. RESULTS: A total of 285 subjects filled out the questionnaires. Participants with significant autistic traits were included into the Broad autism phenotype (BAP) group, while others into the No BAP group. Subjects in the BAP group reported significantly higher ORTO-R scores than others, while no difference was reported for gender, work position, type of diet, age and BMI. Females showed significantly higher ORTO-R scores and lower BMI than males. Older subjects showed a higher BMI. No significant differences in ORTO-R scores were reported depending on type of diet and work position. A decision tree model, with ORTO-R score as dependent variable, revealed in the first step significantly higher ORTO-R scores in the BAP group than in the No BAP group, and in the second step significantly higher ORTO-R scores among females only in the No BAP group. CONCLUSION: Our results further confirm the association between ON and autism spectrum, which seems to overcome the impact of gender in this population. LEVEL OF EVIDENCE: Level V, descriptive study.

Characterization of the interactome profiling of Mycoplasma fermentans DnaK in cancer cells reveals interference with key cellular pathways.

Chaperone proteins are redundant in nature and, to achieve their function, they bind a large repertoire of client proteins. DnaK is a bacterial chaperone protein that recognizes misfolded and aggregated proteins and drives their folding and intracellular trafficking. Some Mycoplasmas are associated with cancers, and we demonstrated that infection with a strain of Mycoplasma fermentans isolated in our lab promoted lymphoma in a mouse model. Its DnaK is expressed intracellularly in infected cells, it interacts with key proteins to hamper essential pathways related to DNA repair and p53 functions and uninfected cells can take-up extracellular DnaK. We profile here for the first time the eukaryotic proteins interacting with DnaK transiently expressed in five cancer cell lines. A total of 520 eukaryotic proteins were isolated by immunoprecipitation and identified by Liquid Chromatography Mass Spectrometry (LC-MS) analysis. Among the cellular DnaK-binding partners, 49 were shared between the five analyzed cell lines, corroborating the specificity of the interaction of DnaK with these proteins. Enrichment analysis revealed multiple RNA biological processes, DNA repair, chromatin remodeling, DNA conformational changes, protein-DNA complex subunit organization, telomere organization and cell cycle as the most significant ontology terms. This is the first study to show that a bacterial chaperone protein interacts with key eukaryotic components thus suggesting DnaK could become a perturbing hub for the functions of important cellular pathways. Given the close interactions between bacteria and host cells in the local microenvironment, these results provide a foundation for future mechanistic studies on how bacteria interfere with essential cellular processes.

Gut Microbiota and COVID-19: Potential Implications for Disease Severity.

The SARS-CoV-2 pandemic resulted in an unprecedented global crisis. SARS-CoV-2 primarily causes lung infection trough the binding of the virus with the ACE-2 cell receptor located on the surface of the alveolar epithelial cells. Notably, ACE-2 cell receptors are also expressed in the epithelial cells of the intestinal tract (GI). Recent data showed that the microbial communities of the GI might act as local and systematic inflammatory modulators. Gastrointestinal symptoms, including diarrhea, are frequently observed in infected individuals, and recent released data indicate that SARS-CoV-2 may also spread by fecal-oral transmission. Moreover, the gut microbiota's ecosystem can regulate and be regulated by invading pathogens, including viruses, facilitating an effective immune response, which in turn results in less severe diseases. In this regard, increased SARS-CoV-2 mortality and morbidities appear to be frequently observed in elderly immunocompromised patients and in people with essential health problems, such as diabetes, who, indeed, tend to have a less diverse gut microbiota (dysbiosis). Therefore, it is important to understand how the interaction between the gut microbiota and SARS-CoV-2 might shape the intensity of the infection and different clinical outcomes. Here, we provide insights into the current knowledge of dysbiosis during SARS-CoV-2 infection and methods that may be used to re-establish a more correct microbiota composition.