Polycystic Ovary Syndrome and COVID-19.

Polycystic ovary syndrome (PCOS) is generally characterized by hyperandrogenism, obesity, chronic low-grade inflammation, abnormalities in carbohydrate and lipid metabolism, vit. D deficiency and gut microbiota dysbiosis. Each of the aforementioned disturbances might be considered as a risk factor for increased SARS-CoV-2 susceptibility and more severe COVID-19 infection in women with PCOS. Hyperandrogenism is thought to play an essential role for determining the grade of susceptibility as well as the risk of severe COVID-19 infection in PCOS. It could be explained by the expression of a specific cellular co-receptor - transmembrane serine protease-2 (TMPRSS2), the process of androgen-dependent immune modulation and that of the stimulated renin-angiotensin system (RAS). Android obesity, commonly seen in PCOS, represents a condition of chronic low-grade inflammation that leads to the development of immune dysfunction and increased sensitivity to SARS-CoV-2 among the carriers of this syndrome. In addition, vit. D deficiency and gut dysbiosis have been described as other potential pathophysiological factors contributing to an increased risk for severe COVID-19 in women with PCOS.Copyright © 2022 Medical Information Center. All rights reserved.

Effects of Gut Microbiome Modulation on Reducing Adverse Health Outcomes among Elderly and Diabetes Patients during the COVID-19 Pandemic: A Randomised, Double-Blind, Placebo-Controlled Trial (IMPACT Study).

Gut microbiota is believed to be a major determinant of health outcomes. We hypothesised that a novel oral microbiome formula (SIM01) can reduce the risk of adverse health outcomes in at-risk subjects during the coronavirus disease 2019 (COVID-19) pandemic. In this single-centre, double-blind, randomised, placebo-controlled trial, we recruited subjects aged ≥65 years or with type two diabetes mellitus. Eligible subjects were randomised in a 1:1 ratio to receive three months of SIM01 or placebo (vitamin C) within one week of the first COVID-19 vaccine dose. Both the researchers and participants were blinded to the groups allocated. The rate of adverse health outcomes was significantly lower in the SIM01 group than the placebo at one month (6 [2.9%] vs. 25 [12.6], p < 0.001) and three months (0 vs. 5 [3.1%], p = 0.025). At three months, more subjects who received SIM01 than the placebo reported better sleep quality (53 [41.4%] vs. 22 [19.3%], p < 0.001), improved skin condition (18 [14.1%] vs. 8 [7.0%], p = 0.043), and better mood (27 [21.2%] vs. 13 [11.4%], p = 0.043). Subjects who received SIM01 showed a significant increase in beneficial Bifidobacteria and butyrate-producing bacteria in faecal samples and strengthened the microbial ecology network. SIM01 reduced adverse health outcomes and restored gut dysbiosis in elderly and diabetes patients during the COVID-19 pandemic.

Polycystic Ovary Syndrome and COVID-19.

Polycystic ovary syndrome (PCOS) is generally characterized by hyperandrogenism, obesity, chronic low-grade inflammation, abnormalities in carbohydrate and lipid metabolism, vit. D deficiency and gut microbiota dysbiosis. Each of the aforementioned disturbances might be considered as a risk factor for increased SARS-CoV-2 susceptibility and more severe COVID-19 infection in women with PCOS. Hyperandrogenism is thought to play an essential role for determining the grade of susceptibility as well as the risk of severe COVID-19 infection in PCOS. It could be explained by the expression of a specific cellular co-receptor - transmembrane serine protease-2 (TMPRSS2), the process of androgen-dependent immune modulation and that of the stimulated renin-angiotensin system (RAS). Android obesity, commonly seen in PCOS, represents a condition of chronic low-grade inflammation that leads to the development of immune dysfunction and increased sensitivity to SARS-CoV-2 among the carriers of this syndrome. In addition, vit. D deficiency and gut dysbiosis have been described as other potential pathophysiological factors contributing to an increased risk for severe COVID-19 in women with PCOS.Copyright © 2022 Medical Information Center. All rights reserved.

Polycystic Ovary Syndrome and COVID-19.

Polycystic ovary syndrome (PCOS) is generally characterized by hyperandrogenism, obesity, chronic low-grade inflammation, abnormalities in carbohydrate and lipid metabolism, vit. D deficiency and gut microbiota dysbiosis. Each of the aforementioned disturbances might be considered as a risk factor for increased SARS-CoV-2 susceptibility and more severe COVID-19 infection in women with PCOS. Hyperandrogenism is thought to play an essential role for determining the grade of susceptibility as well as the risk of severe COVID-19 infection in PCOS. It could be explained by the expression of a specific cellular co-receptor - transmembrane serine protease-2 (TMPRSS2), the process of androgen-dependent immune modulation and that of the stimulated renin-angiotensin system (RAS). Android obesity, commonly seen in PCOS, represents a condition of chronic low-grade inflammation that leads to the development of immune dysfunction and increased sensitivity to SARS-CoV-2 among the carriers of this syndrome. In addition, vit. D deficiency and gut dysbiosis have been described as other potential pathophysiological factors contributing to an increased risk for severe COVID-19 in women with PCOS.Copyright © 2022 Medical Information Center. All rights reserved.

Probiotics and immunity: An overview

Recent outbreak of novel coronavirus COVID 19 as pandemic has threatened mankind and revealed the drawbacks in medical science. Finding innovative ways to treat a disease without generating resistance in pathogens is the need of the hour. Probiotics are commensal microorganisms that reside in the body and confer health benefits to the host. Till date, they have been used merely as food supplement that would enhance digestion. But research shows that they also have effects on the immune system of their host and can be used effectively as an immunomodulator in several diseases like bacterial, viral, cancerous, and autoimmune disorders. This chapter gives a brief insight into the role played by probiotics in enhancing immune response against the cited diseases. © 2023 Elsevier Inc. All rights reserved.

Association between Gut Microbiota and SARS-CoV-2 Infection and Vaccine Immunogenicity.

Gut microbiota is increasingly recognized to play a pivotal role in various human physiological functions and diseases. Amidst the COVID-19 pandemic, research has suggested that dysbiosis of the gut microbiota is also involved in the development and severity of COVID-19 symptoms by regulating SARS-CoV-2 entry and modulating inflammation. Previous studies have also suggested that gut microbiota and their metabolites could have immunomodulatory effects on vaccine immunogenicity, including influenza vaccines and oral rotavirus vaccines. In light of these observations, it is possible that gut microbiota plays a role in influencing the immune responses to COVID-19 vaccinations via similar mechanisms including effects of lipopolysaccharides, flagellin, peptidoglycan, and short-chain fatty acids. In this review, we give an overview of the current understanding on the role of the gut microbiota in COVID-19 manifestations and vaccine immunogenicity. We then discuss the limitations of currently published studies on the associations between gut microbiota and COVID-19 vaccine outcomes. Future research directions shall be focused on the development of microbiota-based interventions on improving immune response to SARS-CoV-2 infection and vaccinations.

Bacteriophage Cocktails in the Post-COVID Rehabilitation.

Increasing evidence suggests that gut dysbiosis is associated with coronavirus disease 2019 (COVID-19) infection and may persist long after disease resolution. The excessive use of antimicrobials in patients with COVID-19 can lead to additional destruction of the microbiota, as well as to the growth and spread of antimicrobial resistance. The problem of bacterial resistance to antibiotics encourages the search for alternative methods of limiting bacterial growth and restoring the normal balance of the microbiota in the human body. Bacteriophages are promising candidates as potential regulators of the microbiota. In the present study, two complex phage cocktails targeting multiple bacterial species were used in the rehabilitation of thirty patients after COVID-19, and the effectiveness of the bacteriophages against the clinical strain of Klebsiella pneumoniae was evaluated for the first time using real-time visualization on a 3D Cell Explorer microscope. Application of phage cocktails for two weeks showed safety and the absence of adverse effects. An almost threefold statistically significant decrease in the anaerobic imbalance ratio, together with an erythrocyte sedimentation rate (ESR), was detected. This work will serve as a starting point for a broader and more detailed study of the use of phages and their effects on the microbiome.

Effects of enhanced hygiene measures on severe diarrhea and anastomotic leak after colorectal cancer surgery: the experience of a tertiary referral hospital in China.

Background: The 2019 novel coronavirus (COVID-19) global pandemic has greatly changed the mode of hospital admissions. This study summarized and analyzed the incidence of severe diarrhea and anastomotic leakage during different periods for colorectal cancer surgery. Methods: From January 2017 to September 2020, 2,619 colorectal operations were performed in Peking Union Medical College Hospital. In contrast with previous years, enhanced hand hygiene training, more frequent ventilation of the wards, and separate bed treatments for patients were implemented in 2020. Data on incidence of severe diarrhea and anastomotic leakage were retrieved and collected. Results: The number of cases of severe diarrhea after colorectal surgery was 32 (4.60%), 24 (3.33%), 32 (3.83%), and 11 (2.99%) in 2017, 2018, 2019, and 2020 respectively, while the incidence of anastomotic leakage was 3.30% (23/696), 3.75% (27/720), 2.87% (24/835), and 2.17% (8/368), respectively. There was no significant difference in the incidence of postoperative severe diarrhea or anastomotic leakage across the various years. Conclusions: The number of colorectal surgeries in 2020 was significantly decreased due to the COVID-19 pandemic. Among the different years, no difference was observed regarding the incidence of postoperative flora disorder or anastomosis leakage. Enhanced hygiene measures during the COVID-19 epidemic partially contributed to the decrease of severe diarrhea and anastomotic leakage.

Impact of COVID-19 and Antibiotic Treatments on Gut Microbiome: A Role for Enterococcus spp.

OBJECTIVE: Several studies showed the substantial use of antibiotics and increased risk of antimicrobial resistant infections in patients with COVID-19. The impact of COVID-19-related treatments and antibiotics on gut dysbiosis has not been clarified. DESIGN: The prospective cohort study included hospitalized COVID-19 patients (April-December 2020). The gut microbiome composition was analysed by 16S sequencing. The gut diversity and changes in opportunistic bacteria (OBs) or symbionts were analysed according to clinical parameters, laboratory markers of disease progression, type of non-antibiotic COVID-19 treatments (NACT) and type, WHO AWaRe group, and duration of antibiotic therapy (AT). RESULTS: A total of 82 patients (mean age 66 ± 13 years, 70% males) were enrolled. The relative abundance of Enterococcus was significantly correlated with duration of hospitalization, intensive care unit stay, O2 needs, and D-dimer, ferritin, and IL-6 blood levels. The presence of Enterococcus showed the highest number of correlations with NACT, AT, and AT + NACT (e.g., hydroxychloroquine ± lopinavir/ritonavir) and increased relative abundance with AWaRe Watch/Reserve antibiotics, AT duration, and combinations. Abundance of Dorea, Agathobacter, Roseburia, and Barnesiella was negatively correlated with AT and corticosteroids use. Patients with increased IL-6, D-dimer, and ferritin levels receiving AT were more likely to show dysbiosis with increased abundance of Enterococcus and Bilophila bacteria and decreased abundance of Roseburia compared with those not receiving AT. CONCLUSION: Microbiome diversity is affected by COVID-19 severity. In this context, antibiotic treatment may shift the gut microbiome composition towards OBs, particularly Enterococcus. The impact of treatment-driven dysbiosis on OBs infections and long-term consequences needs further study to define the role of gut homeostasis in COVID-19 recovery and inform targeted interventions.

Mechanisms Leading to Gut Dysbiosis in COVID-19: Current Evidence and Uncertainties Based on Adverse Outcome Pathways.

Alteration in gut microbiota has been associated with COVID-19. However, the underlying mechanisms remain poorly understood. Here, we outlined three potential interconnected mechanistic pathways leading to gut dysbiosis as an adverse outcome following SARS-CoV-2 presence in the gastrointestinal tract. Evidence from the literature and current uncertainties are reported for each step of the different pathways. One pathway investigates evidence that intestinal infection by SARS-CoV-2 inducing intestinal inflammation alters the gut microbiota. Another pathway links the binding of viral S protein to angiotensin-converting enzyme 2 (ACE2) to the dysregulation of this receptor, essential in intestinal homeostasis-notably for amino acid metabolism-leading to gut dysbiosis. Additionally, SARS-CoV-2 could induce gut dysbiosis by infecting intestinal bacteria. Assessing current evidence within the Adverse Outcome Pathway framework justifies confidence in the proposed mechanisms to support disease management and permits the identification of inconsistencies and knowledge gaps to orient further research.

Symptomatology and microbiology of the gastrointestinal tract in post-COVID conditions.

Post-COVID conditions, also known as post-acute sequelae of SARS-CoV-2 (PASC), refer to the persistence of symptoms in COVID-19 long-haulers. Various manifestations of post-COVID conditions are general symptoms and/or manifestations of damage in multiple organs. Besides, SARS-CoV-2 can involve the gastrointestinal tract, resulting in sequelae such as diarrhea, abdominal pain, nausea, anorexia, vomiting, constipation, abdominal distension, acid reflux, and/or gastrointestinal bleeding. Previous investigations point to SARS-CoV-2 entry into enterocytes enhances by the angiotensin-converting enzyme 2 (ACE2) receptors. Interestingly, ACE2 receptors are abundantly expressed in the gut, implying infection with SARS-CoV-2 might occur through this route as well as in the respiratory tract. According to mounting evidence, SARS-CoV-2 RNA has been identified in fecal specimens of patients with COVID-19 during and beyond the acute phase. In addition, studies have shown gut microbiome composition is altered in patients with PASC, hence, another putative mechanism linked to gastrointestinal symptoms is gut dysbiosis. The presence of the gut-lung axis in COVID-19 might have major implications for disease pathogenesis and treatment. This review discussed the prevalence of gastrointestinal symptoms and pathophysiology underlying possible infection of the gut in patients with PASC. Also, SARS-COV-2 induced NLRP3 inflammasome-dependent inflammatory pathways are briefly addressed.

The pathophysiological mechanisms of COVID-19 and host immunity, with emphasis on the dysbiosis of the lung and gut microbiomes and pregnancy.

The coronavirus 2019 (COVID-19) pandemic is a health and economic crisis. It has also highlighted human relational problems, such as racism and conflicts between nations. Although vaccination programs against the severe respiratory syndrome coronavirus 2 (SARS-CoV-2) have started worldwide, the pandemic is ongoing, and people are struggling. The mechanism of disease severity in COVID-19 is multifactorial, complicated, and affected by viral pathogenesis. For example, monocyte dysfunction due to aging and respiratory and gut dysbiosis influence the host's immunity against SARS-CoV-2 including helper T-cell imbalance and viral clearance reduction, leading to accelerated disease progression in older patients or those with underlying diseases. The different immune responses against SARS-CoV-2 also contribute to various radiological findings, including that of acute respiratory distress syndrome, which is associated with high mortality, especially in patients susceptible to disease progression. We aimed to review the pathophysiological mechanisms involved in COVID-19, with emphasis on the altered microbiome in the lung and gut, and the different radiological findings in different patient groups, such as younger adults and pregnant women.

Understanding the mechanism underlying the anti-diabetic effect of dietary component: a focus on gut microbiota.

Diabetes has become one of the biggest non-communicable diseases and threatens human health worldwide. The management of diabetes is a complex and multifaceted process including drug therapy and lifestyle interventions. Dietary components are essential for both diabetes management and health and survival of trillions of the gut microbiota (GM). Herein, we will discuss the relationship between diets and GM, the mechanism linking diabetes and gut dysbiosis, and the effects of dietary components (nutrients, phytochemicals, probiotics, food additives, etc.) on diabetes from the perspective of modulating GM. The GM of diabetic patients differs from that of health individuals and GM disorder contributes to the onset and maintenance of diabetes. Studies in humans and animal models consolidate that dietary component is a key regulator of diabetes and increasing evidence suggests that the alteration of GM plays a salient role in dietary interventions for diabetes. Given that diabetes is a major public health issue, especially that diabetes is linked with a high risk of mortality from COVID-19, this review provides compelling evidence for that targeting GM by dietary components is a promising strategy, and offers new insights into potential preventive or therapeutic approaches (dietary and pharmacological intervention) for the clinical management of diabetes.

Immune Mechanisms of Plaque Instability.

Inflammation crucially drives atherosclerosis from disease initiation to the emergence of clinical complications. Targeting pivotal inflammatory pathways without compromising the host defense could compliment therapy with lipid-lowering agents, anti-hypertensive treatment, and lifestyle interventions to address the substantial residual cardiovascular risk that remains beyond classical risk factor control. Detailed understanding of the intricate immune mechanisms that propel plaque instability and disruption is indispensable for the development of novel therapeutic concepts. In this review, we provide an overview on the role of key immune cells in plaque inception and progression, and discuss recently identified maladaptive immune phenomena that contribute to plaque destabilization, including epigenetically programmed trained immunity in myeloid cells, pathogenic conversion of autoreactive regulatory T-cells and expansion of altered leukocytes due to clonal hematopoiesis. From a more global perspective, the article discusses how systemic crises such as acute mental stress or infection abruptly raise plaque vulnerability and summarizes recent advances in understanding the increased cardiovascular risk associated with COVID-19 disease. Stepping outside the box, we highlight the role of gut dysbiosis in atherosclerosis progression and plaque vulnerability. The emerging differential role of the immune system in plaque rupture and plaque erosion as well as the limitations of animal models in studying plaque disruption are reviewed.

COVID-19 and gut dysbiosis, understanding the role of probiotic supplements in reversing gut dysbiosis and immunity

In December 2019, an outbreak of novel beta-coronavirus started in Wuhan, China, spread globally as coronavirus disease 2019 (COVID-19) pandemic and is still underway. The causative agent for COVID-19 identified as a novel strain of beta coronavirus named nSARS-CoV-2. The nSARS-CoV-2 primarily targets the respiratory tract and results in severe acute respiratory distress (ARDS), leading to the collapse of the respiratory tract. The virus internalizes primarily via ACEII receptor, and many tissues reported a significant level of expression of ACEII receptor including lungs, hearts, kidneys, and gastrointestinal tract. The clinical manifestations of COVID-19 are diverse, but growing evidence suggests that gut dysbiosis is one of them and poses a threat to native immunity. The human microbial ecology plays a vital role in human physiology, including building immunity. The gastrointestinal tract (GIT) habitats trillions of beneficial microbes’ precisely bacterial species synchronize with human physiology and remain symbiotic. On the contrary, harmful microbiota seeks an opportunity to break the equilibrium failure of balance between beneficial and detrimental human gut microbiota results in impaired physiology and immunity. The grown research evidence demonstrated that infection caused by the nSARS-CoV-2 result in moderate to severe diarrheal outcomes. The diarrheal conditions in COVID-19 patients are due to alteration of gut microbial ecology. The management of COVID-19 requires specialized therapeutics along with a series of nutraceuticals. Probiotics remain vital nutrient supplements in COVID-19 management, offer relief in diarrhea and improve/restore immunity. This study uses available data/findings to emphasize an association between COVID-19 and gut dysbiosis. The study also provides a scientific basis of impaired immunity during gut dysbiosis in COVID-19 and how probiotics help restore and improve impaired immunity and diarrhea.

SARS-CoV-2 infection in nonhuman primates alters the composition and functional activity of the gut microbiota.

The current pandemic of coronavirus disease (COVID) 2019 constitutes a global public health issue. Regarding the emerging importance of the gut-lung axis in viral respiratory infections, analysis of the gut microbiota's composition and functional activity during a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection might be instrumental in understanding and controling COVID 19. We used a nonhuman primate model (the macaque), that recapitulates mild COVID-19 symptoms, to analyze the effects of a SARS-CoV-2 infection on dynamic changes of the gut microbiota. 16S rRNA gene profiling and analysis of ß diversity indicated significant changes in the composition of the gut microbiota with a peak at 10-13 days post-infection (dpi). Analysis of bacterial abundance correlation networks confirmed disruption of the bacterial community at 10-13 dpi. Some alterations in microbiota persisted after the resolution of the infection until day 26. Some changes in the relative bacterial taxon abundance associated with infectious parameters. Interestingly, the relative abundance of Acinetobacter (Proteobacteria) and some genera of the Ruminococcaceae family (Firmicutes) was positively correlated with the presence of SARS-CoV-2 in the upper respiratory tract. Targeted quantitative metabolomics indicated a drop in short-chain fatty acids (SCFAs) and changes in several bile acids and tryptophan metabolites in infected animals. The relative abundance of several taxa known to be SCFA producers (mostly from the Ruminococcaceae family) was negatively correlated with systemic inflammatory markers while the opposite correlation was seen with several members of the genus Streptococcus. Collectively, SARS-CoV-2 infection in a nonhuman primate is associated with changes in the gut microbiota's composition and functional activity.

SARS-CoV-2 infection, gut dysbiosis, and heterogeneous clinical results of hydroxychloroquine on COVID-19 therapy-Is there a link?

Clinical manifestations of the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can include gastrointestinal signals and symptoms. Individuals with previous clinical conditions that usually enroll gut dysbiosis have been identified as being at high risk to develop more severe infectious phenotypes. Actually, intestinal dysbiosis has been observed in infected patients and potentially linked to systemic hyperinflammation. These observations suggest that a previous gut dysbiosis may be aggravated by SARS-CoV-2 infection and related to progression of the coronavirus disease 2019 (COVID-19) into more severe stages. While COVID-19's pathophysiology is not fully understood, it seems relevant to consider the interactions of candidate therapeutic drugs with the host, gut microbiota, and SARS-CoV-2. Here we summarize scientific evidence supporting the potential relevance of these interactions and suggest that unfavorable clinical data on hydroxychloroquine administration in COVID-19 may have been influenced by the dose provided and its impact on gut dysbiosis. The proposition is based on preliminary data on gut microbiota composition from individuals with inactive systemic lupus erythematosus under exclusive continuous hydroxychloroquine treatment, displaying a direct correlation between drug doses and markers typically associated with gut dysbiosis.

Does intestinal dysbiosis contribute to an aberrant inflammatory response to severe acute respiratory syndrome coronavirus 2 in frail patients?

In a few months, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has become the main health problem worldwide. Epidemiologic studies revealed that populations have different vulnerabilities to SARS-CoV-2. Severe outcomes of the coronavirus disease 2019 (COVID-19) with an increased risk of death are observed in patients with metabolic syndrome, as well as diabetic and heart conditions (frail population). Excessive proinflammatory cytokine storm could be the main cause of increased vulnerability in this frail population. In patients with diabetes and/or heart disease, a low inflammatory state is often associated with gut dysbiosis. The increase amount of microbial metabolites (i.e., trimethylamine N-oxide and lipopolysaccharide), which generate an inflammatory microenvironment, is probably associated with an improved risk of severe illness from COVID-19. Nutritional interventions aimed at restoring the gut microbial balance could represent preventive strategies to protect the frail population from COVID-19. This narrative review presents the possible molecular mechanisms by which intestinal dysbiosis that enhances the inflammatory state could promote the spread of SARS-CoV-2 infection. Some nutritional strategies to counteract inflammation in frail patients are also analyzed.