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SARS-CoV-2 and immune-microbiome interactions: Lessons from respiratory viral infections.
Cyprian, F, Sohail, MU, Abdelhafez, I, Salman, S, Attique, Z, Kamareddine, L, Al-Asmakh, M
International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases. 2021;105:540-550
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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an enveloped RNA beta-coronavirus. This virus caused the coronavirus disease 2019 (COVID-19) pandemic. The aim of this review was to investigate the relationship between microbiota, immunity, and COVID-19, with particular focus on how microbiome-associated immune crosstalk can shape outcome of COVID-19. The study included 118 articles which investigated or reviewed COVID-19 or coronavirus and the microbiome of the gut or respiratory tract. Findings indicate that: - an over-activated immune system leads to massive pulmonary damage in COVID-19 patients. - the effect of aging and comorbidities, and the use of antibiotics have an effect on the diversity of the microbiota. - the milieu of gut flora can exert influence on pulmonary immune responses. - a unique cross-talk exists between the pulmonary and gut microbial compartments. Authors conclude by highlighting the need of further studies that delineate the role of the microbiota and their products in the immune dysregulation observed in SARS-CoV-2 infections.
Abstract
By the beginning of 2020, infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) had rapidly evolved into an emergent worldwide pandemic, an outbreak whose unprecedented consequences highlighted many existing flaws within public healthcare systems across the world. While coronavirus disease 2019 (COVID-19) is bestowed with a broad spectrum of clinical manifestations, involving the vital organs, the respiratory system transpires as the main route of entry for SARS-CoV-2, with the lungs being its primary target. Of those infected, up to 20% require hospitalization on account of severity, while the majority of patients are either asymptomatic or exhibit mild symptoms. Exacerbation in the disease severity and complications of COVID-19 infection have been associated with multiple comorbidities, including hypertension, diabetes mellitus, cardiovascular disorders, cancer, and chronic lung disease. Interestingly, a recent body of evidence indicated the pulmonary and gut microbiomes as potential modulators for altering the course of COVID-19, potentially via the microbiome-immune system axis. While the relative concordance between microbes and immunity has yet to be fully elucidated with regards to COVID-19, we present an overview of our current understanding of COVID-19-microbiome-immune cross talk and discuss the potential contributions of microbiome-related immunity to SARS-CoV-2 pathogenesis and COVID-19 disease progression.
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Berberine reduces circulating inflammatory mediators in patients with severe COVID-19.
Zhang, BY, Chen, M, Chen, XC, Cao, K, You, Y, Qian, YJ, Yu, WK
The British journal of surgery. 2021;108(1):e9-e11
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Berberine has a long history in traditional Chinese medicine for the treatment of diarrhoea and gastroenteritis owing to its antimicrobial, antimotility and antisecretory properties. The aim of this study was to examine the effect of berberine on laboratory parameters in patients who have been hospitalised due to COVID-19. This study enrolled prospectively 39 patients with severe COVID-19 who were hospitalized, of which 18 patients were allocated to the berberine group and 17 to the control group. Patients in the berberine group were given berberine plus routine therapy within 14 days of admission, and those in the control group received only routine therapy. Results indicate that there wasn’t any significant difference between the two groups in relation to the laboratory parameters namely interleukin-6, tumour necrosis factor-alpha, C-reactive protein, procalcitonin and white blood cells levels within 14 days. In subgroup analyses of patients with diarrhoea, berberine significantly improved the changes in interleukin-6, tumour necrosis factor-alpha and C-reactive protein. Authors conclude that it is unclear whether berberine has any antiviral effect on SARS-CoV-2, and further experiments are needed to clarify this.
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Understanding Viral Infection Mechanisms and Patient Symptoms for the Development of COVID-19 Therapeutics.
Choi, HM, Moon, SY, Yang, HI, Kim, KS
International journal of molecular sciences. 2021;22(4)
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The outbreak of a novel coronavirus was reported in Wuhan, in the Hubei province of China, in December 2019. This virus was officially designated as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) because of its phylogenetic and taxonomic similarities to other coronaviruses. The aim of this review was to understand the viral infection mechanisms of SARS-CoV-2, the clinical features of Covid-19 and the mechanisms through which Covid-19 can be effectively treated with existing drugs. Literature shows that: • SARS-CoV-2 is usually transmitted by inhalation or contact with infected droplets. Inhaled droplets or aerosol carrying the virus then infect and spread through the respiratory tracts. • Severe inflammatory response is a remarkable feature of Covid-19 symptoms. This is caused by delayed viral clearance, which induces chronic systemic inflammation and widespread tissue damage, even leading to cytokine storms. • The incubation period is generally 5-6 days, but it ranges from one day to as much as two weeks. • Interstitial pneumonia and subsequent acute respiratory distress syndrome are the leading causes of death in patients with Covid-19. • There is no licensed treatment for Covid-19, only a combination of antiviral and anti-inflammatory drug treatments are being used. Authors conclude that their finding may provide new insights into the development of therapeutics by understanding the various clinical and basic research studies currently underway.
Abstract
Coronavirus disease 2019 (COVID-19), caused by the SARS-CoV-2 virus, has become a worldwide pandemic. Symptoms range from mild fever to cough, fatigue, severe pneumonia, acute respiratory distress syndrome (ARDS), and organ failure, with a mortality rate of 2.2%. However, there are no licensed drugs or definitive treatment strategies for patients with severe COVID-19. Only antiviral or anti-inflammatory drugs are used as symptomatic treatments based on clinician experience. Basic medical researchers are also trying to develop COVID-19 therapeutics. However, there is limited systematic information about the pathogenesis of COVID-19 symptoms that cause tissue damage or death and the mechanisms by which the virus infects and replicates in cells. Here, we introduce recent knowledge of time course changes in viral titers, delayed virus clearance, and persistent systemic inflammation in patients with severe COVID-19. Based on the concept of drug reposition, we review which antiviral or anti-inflammatory drugs can effectively treat COVID-19 patients based on progressive symptoms and the mechanisms inhibiting virus infection and replication.
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Probiotics in Prevention and Treatment of COVID-19: Current Perspective and Future Prospects.
Kurian, SJ, Unnikrishnan, MK, Miraj, SS, Bagchi, D, Banerjee, M, Reddy, BS, Rodrigues, GS, Manu, MK, Saravu, K, Mukhopadhyay, C, et al
Archives of medical research. 2021;52(6):582-594
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The novel coronavirus pandemic of 2019 (COVID-19), an emerging infectious disease, is caused by multiple strains of Severe Acute Respiratory Syndrome Coronavirus-2. The main aim of this study was to outline the potential role of probiotics in fighting the COVID-19. This study focuses on recent evidence on the association between microbiota, probiotics, and COVID-19, the role of probiotics as an immune-modulator and antiviral agent. Findings support probiotics’ role in regulating the immune system, suggesting a definitive role for probiotics in viral infections. Thus, probiotics supplementation could reduce the severity of COVID-19 morbidity and mortality. Authors conclude that supplementation of probiotics in high risk and severely ill patients, and frontline health workers, may help to limit the infection and flatten the COVID-19 curve. However, further studies should be conducted for more conclusive evidence.
Abstract
Saving lives and flattening the curve are the foremost priorities during the ongoing pandemic spread of SARS-CoV-2. Developing cutting-edge technology and collating available evidence would support frontline health teams. Nutritional adequacy improves general health and immunity to prevent and assuage infections. This review aims to outline the potential role of probiotics in fighting the COVID-19 by covering recent evidence on the association between microbiota, probiotics, and COVID-19, the role of probiotics as an immune-modulator and antiviral agent. The high basic reproduction number (R0) of SARS-CoV-2, absence of conclusive remedies, and the pleiotropic effect of probiotics in fighting influenza and other coronaviruses together favour probiotics supplements. However, further support from preclinical and clinical studies and reviews outlining the role of probiotics in COVID-19 are critical. Results are awaited from many ongoing clinical trials investigating the benefits of probiotics in COVID-19.
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Potential role of microbiome in Chronic Fatigue Syndrome/Myalgic Encephalomyelits (CFS/ME).
Lupo, GFD, Rocchetti, G, Lucini, L, Lorusso, L, Manara, E, Bertelli, M, Puglisi, E, Capelli, E
Scientific reports. 2021;11(1):7043
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Chronic Fatigue Syndrome/Myalgic Encephalomyelits (CFS/ME) is a severe multisystemic disease. The main symptom is persistent unexplained fatigue, it has inflammatory symptoms, is characterized by an abnormal immune response and dysfunction of energy metabolism. Recent studies suggest strong correlations between dysbiosis and other conditions such as intestinal disorders, autoimmune conditions, cancer and several neurological disorders. In the case of CFS/ME, some studies have shown an altered composition of the gut and oral microbiomes. In this study the oral and intestinal bacterial composition of CFS/ME patients were analysed and compared to a group of relatives and to a control population outside the families. This was to identify a possible effect of lifestyle habits and a microbial profile of CFS/ME syndrome. The study showed significant variations in both the intestinal and oral bacteria composition between CFS/ME patients, their relatives and external controls. There is a lot of interesting detail about the levels of specific bacteria in each group. Further studies are needed to better understand if the microbial composition changes are cause or consequence of the onset of CFS/ME and if they are related to any of the several secondary symptoms.
Abstract
Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) is a severe multisystemic disease characterized by immunological abnormalities and dysfunction of energy metabolism. Recent evidences suggest strong correlations between dysbiosis and pathological condition. The present research explored the composition of the intestinal and oral microbiota in CFS/ME patients as compared to healthy controls. The fecal metabolomic profile of a subgroup of CFS/ME patients was also compared with the one of healthy controls. The fecal and salivary bacterial composition in CFS/ME patients was investigated by Illumina sequencing of 16S rRNA gene amplicons. The metabolomic analysis was performed by an UHPLC-MS. The fecal microbiota of CFS/ME patients showed a reduction of Lachnospiraceae, particularly Anaerostipes, and an increased abundance of genera Bacteroides and Phascolarctobacterium compared to the non-CFS/ME groups. The oral microbiota of CFS/ME patients showed an increase of Rothia dentocariosa. The fecal metabolomic profile of CFS/ME patients revealed high levels of glutamic acid and argininosuccinic acid, together with a decrease of alpha-tocopherol. Our results reveal microbial signatures of dysbiosis in the intestinal microbiota of CFS/ME patients. Further studies are needed to better understand if the microbial composition changes are cause or consequence of the onset of CFS/ME and if they are related to any of the several secondary symptoms.
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An algorithm for differentiating food antigen-related gastrointestinal symptoms.
Rostami, K, Bold, J, Ismail Ali, J, Parr, A, Dieterich, W, Zopf, Y, Htoo, A, Rostami-Nejad, M, Danciu, M
Gastroenterology and hepatology from bed to bench. 2021;14(1):8-16
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Irritable bowel syndrome (IBS) is a collection of gastrointestinal symptoms. Due to multiple etiologies, the pathogenesis of IBS is poorly understood. The aim of this audit was to assess the outcomes achieved using a lactose and gluten-free diet clinical intervention in patients traditionally diagnosed with IBS. This study was an audit of outcomes from the records of 149 patients presenting with IBS symptoms at secondary and tertiary Gastroenterology outpatients in two UK hospitals. This audit has demonstrated that more than 70% of patients presenting with IBS symptoms improved by following a diet eliminating lactose and gluten containing grains (improvement for >30% in their symptoms). The success of the elimination diet did not seem to be correlated with the body mass index (BMI). The best outcome was recorded in patients with normal BMI and also in the overweight group. Patients with higher BMI >30 or low below 18 also responded well to nutrition therapy. In conclusion, multidisciplinary team management and implementation of detailed nutrition therapy using the audit algorithm might prove to be both cost effective and efficacious a treatment option in IBS.
Abstract
AIM: The aim of this clinical audit was to assess patient-reported outcomes on the effect of dietary intervention, to enhance our understanding of possible treatment options in irritable bowel syndrome (IBS). BACKGROUND A large number of food-related gastro-intestinal disorders have been attributed to IBS for decades. METHODS Patient-reported outcomes from the records of 149 IBS patients treated at secondary and tertiary Gastroenterology outpatients in two UK hospitals between January 2014 and July 2016 were audited. Patients all presented with symptoms fulfilling Rome III-IV criteria for IBS had negative coeliac serology and did not have other gastrointestinal (GI) conditions. A modified version of a low FODMAP diet had been recommended (gluten and lactose free diet (G/LFD)) and was implemented for 6 weeks. Outcomes and dietary adherence were recorded during outpatient's consultations. RESULTS A total of 134 patients complied with the diet optimally. The majority had an improvement rate >70% and continued with the diet. Fifty-three percent became completely or almost asymptomatic, while 27.6% had a poor response to the diet (scoring < 30%) to G/LFD. The improvement was excellent in patients with normal BMI and good in overweight and obese and where BMI <18. Over 50% did not require any follow-up within 12 months. CONCLUSION Although it is unclear whether symptoms are triggered by gluten, fructans or lactose, elimination of gluten and lactose proved to be an effective treatment in patients with IBS. Multidisciplinary team management and implementation of detailed nutrition therapy using the audit algorithm might prove to be both cost effective and efficacious a treatment option in IBS.
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Anxiety, anhedonia and food consumption during the COVID-19 quarantine in Chile.
Landaeta-Díaz, L, González-Medina, G, Agüero, SD
Appetite. 2021;164:105259
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It has been recognised that mechanisms to cope with stress and the inability to feel pleasure can include eating foods high in sugar, carbohydrates, and fat, resulting in obesity. The current Covid-19 pandemic could be causing stress and anxiety to many individuals. This cross-sectional study aimed to determine the role of anxiety and reduced feelings of pleasure on diet and weight during the covid-19 pandemic in 1725 individuals in Chile. The results showed that anxiety levels were related to an increased consumption of sugar-sweetened drinks, fast food, and pastries. However, there was no relationship between lockdown measures due to Covid-19 and feelings of anxiety or reduced feelings of pleasure. Increased portion sizes were also related to anxiety levels. It was concluded that high levels of anxiety were related to increased consumption of unhealthy foods. This study could be used by healthcare professionals to recognise the need to recommend healthy eating habits for the wellbeing of patients who are suffering from anxiety.
Abstract
The current epidemic of COVID-19 has gained attention and highlighted the need for a better understanding of the population's mental health. Diet has been identified as an environmental determinant of mental health. In this regard, it has been suggested that the consumption of palatable foods represents a strategy to mitigate negative emotions, such as anxiety. This study aimed to evaluate the association between symptoms of anxiety and/or anhedonia to food consumption patterns during the period of COVID-19 quarantine in Chile. We conducted a cross-sectional study with non-randomized sampling via an online survey. A total of 1725 responses were collected. Each person self-answered the Beck Anxiety Inventory, Snaith-Hamilton Pleasure Scale for anhedonia, the Food Intake Questionnaire, and questions regarding type and duration of lockdown, as well as body weight and food serving variation. Significant correlations were observed between fried food consumption and self-reported body weight. The subjects who consumed fried food three times a week, had higher weight (63.5%) (χ2 = 48.5 and p < 0.001). Those who ate one and two or more pastries on a week had 1.41 and 1.49, respectively higher odds of reporting increased body weight. We found a relationship anxiety level and sugar-sweetened beverages level (χ2 = 25.5; p 0.013), fast food intake (χ2 = 63.4; p < 0.001), and pastry consumption (χ2 = 37.7; p < 0.001). In conclusion, it is important to monitor the evolution of these findings since they could represent a risk of increased health problems in the future post-lockdown period.
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Eating in the lockdown during the Covid 19 pandemic; self-reported changes in eating behaviour, and associations with BMI, eating style, coping and health anxiety.
Coulthard, H, Sharps, M, Cunliffe, L, van den Tol, A
Appetite. 2021;161:105082
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The Covid-19 pandemic resulted in national lockdowns, which resulted in isolation within people’s homes. This cross-sectional survey examined changes in eating patterns and behaviour during lockdown. Of the 620 participants included in the study, eating higher energy density foods was more common in females with a higher BMI and higher health anxiety. Although there was a change in emotional eating behaviours across the sample as a whole, it was not in the expected direction, with many participants reporting a decrease in emotional eating after the implementation of lockdown. There were also increases in fruit and vegetable consumption and home prepared foods. Many of these behavioural responses were influenced by pre-lockdown tendencies. Therefore, it is important to consider these when understanding coping strategies during lockdown, and how to support clients as we come out of lockdown.
Expert Review
Conflicts of interest:
None
Take Home Message:
- National lockdowns, as seen during the 2020/21 Covid-19 pandemic, impacted eating behaviour and associations with BMI, eating style and health anxiety.
- Given the new nature of this research, it is not clear what impact confounding factors such as food insecurity had on changing eating behaviours.
- Disproportionate risks were seen in certain demographics and in those shielding due to their heightened risk from Covid-19.
- Retrospective and longitudinal studies to monitor the impact of lockdowns on eating behaviour and health anxiety are needed.
Evidence Category:
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A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
The role of eating behaviours and psychological responses during lockdown has become an area of interest, particularly with the uncertainty of going into future lockdowns. With Covid-19, and individual’s responses to it, being a relatively new research topic, there is not yet enough evidence for longitudinal outcomes of the findings in these studies. It is also difficult to ascertain the influence of confounding variables prior to the national lockdown, such as food insecurity, not accounted for due to the unpredictable start to the pandemic. There has also been disproportionate risks between certain demographics and their Covid-19 risk, therefore further research on the impact of this on health anxiety and subsequent eating behaviours is required. This highlights a wider need for continued research on the topic.
Clinical practice applications:
Those who had problematic eating behaviours and higher BMI pre lockdown will need to be supported with healthier coping practices if subsequent lockdowns occur, to prevent health related anxiety and consumption of high energy density foods. Furthermore, those who were shielding in their homes were also more likely to show an increase in emotional eating post lockdown. Therefore, clients who spent a large amount of lockdown shielding will need additional support, to develop coping strategies to prevent risk of emotional eating and health anxiety.
Considerations for future research:
Both retrospective and longitudinal studies monitoring the impact of eating behaviours and health anxiety pre and post lockdown are needed. This will help further the evidence base of the potential role of Covid-19 related health anxiety on eating patterns, coping strategies and dietary choices.
Abstract
The global coronavirus pandemic (Covid 19) resulted in national lockdowns where individuals were asked to isolate in their homes to stop the spread of the disease. Using a cross-sectional survey, the current paper aimed to examine self-reported changes in eating patterns and behaviour during the lockdown in the UK, and associations with BMI, demographic variables, eating styles, health anxiety, food insecurity and coping strategies. Participants (N = 620) were recruited online through social media advertising. The results showed that there were self-reported changes to food consumption during the lockdown across the sample. Increases in consumption of HED (high energy density) snack foods during the lockdown was associated with sex, pre-lockdown eating behaviour (emotional eating and uncontrolled eating), and Covid-specific health anxiety. Increases in positive eating practices such as eating more home prepared foods, and fruits and vegetables, were associated with adaptive coping strategies. Higher emotional eating (EE) during the lockdown was associated with a higher BMI, higher pre-lockdown EE and maladaptive coping strategies. Maladaptive coping strategies moderated the relationship between BMI and EE during the lockdown. In particular a higher BMI was associated with higher EE during the lockdown if an individual also had higher maladaptive coping strategies. These findings suggest that changes to eating behaviour may be part of a wider style of maladaptive or adaptive coping, particularly in those with a history of EE or uncontrolled eating. Preparing individuals to adopt more adaptive coping strategies during lockdown situations may be crucial to improving health during subsequent the lockdown events.
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Brain Neurotransmitter Modulation by Gut Microbiota in Anxiety and Depression.
Huang, F, Wu, X
Frontiers in cell and developmental biology. 2021;9:649103
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The causes of anxiety and depression are unclear, but growing evidence points to a role of the gut microbiota. One possible way that the gut microbiota may have an influence on mental health is through a group of chemical messengers in the brain, known as neurotransmitters. This review summarised the research surrounding neurotransmitters and gut microbiota. The review began by looking at research in animal models and the roles of various neurotransmitters and how they may be influenced by the gut microbiota. The neurotransmitters outlined were serotonin, dopamine, and noradrenaline and it was stated that there is evidence that gut microbiota may be able to influence them alleviating anxiety and/or depression, however there was limited evidence with noradrenaline. It was concluded that there is a close connection between the gut microbiota and anxiety and depression. There is more research needed in humans, as most work has been completed in animal models. This paper could be used by healthcare professionals to understand the role of the gut microbiota in mental health disorders and the importance of gut health in individuals suffering from these.
Abstract
Anxiety and depression are highly prevalent mental illnesses worldwide and have long been thought to be closely associated to neurotransmitter modulation. There is growing evidence indicating that changes in the composition of the gut microbiota are related to mental health including anxiety and depression. In this review, we focus on combining the intestinal microbiota with serotonergic, dopaminergic, and noradrenergic neurotransmission in brain, with special emphasis on the anxiety- and depression-like behaviors in stress-related rodent models. Therefore, we reviewed studies conducted on germ-free rodents, or in animals subjected to microbiota absence using antibiotics, as well as via the usage of probiotics. All the results strongly support that the brain neurotransmitter modulation by gut microbiota is indispensable to the physiopathology of anxiety and depression. However, a lot of work is needed to determine how gut microbiota mediated neurotransmission in human brain has any physiological significance and, if any, how it can be used in therapy. Overall, the gut microbiota provides a novel way to alter neurotransmitter modulation in the brain and treat gut-brain axis diseases, such as anxiety and depression.
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Effects of Microbiota Imbalance in Anxiety and Eating Disorders: Probiotics as Novel Therapeutic Approaches.
Navarro-Tapia, E, Almeida-Toledano, L, Sebastiani, G, Serra-Delgado, M, García-Algar, Ó, Andreu-Fernández, V
International journal of molecular sciences. 2021;22(5)
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The interest in mental health has increased recently. Anxiety and mood disorders are associated with many disabilities and there is a close relationship between eating disorders and anxiety. Although current medical treatments for anxiety disorders are safer than a few decades ago; the effectiveness in some of them has not improved, they have side effects and can cause addiction. Therefore, the development of new tools to restore mental health without the undesired effects is necessary. Recent studies indicate that patients with generalized anxiety or eating disorders (anorexia nervosa, bulimia nervosa, and binge-eating disorders) show a specific gut microbiota profile, and this imbalance can be partially restored after a single or multi-strain probiotic supplementation. The purpose of this review is to look at the main microbial patterns seen in patients with generalized anxiety and/or eating disorders as well as the importance of probiotics as a preventive or a therapeutic tool in these pathologies. The studies reviewed showed an imbalance of microbial communities in patients with anxiety and with eating disorders. The effect of probiotics in reducing anxiety seems to be more effective the higher the baseline anxiety level of the individual. For eating disorders, the correction of dysbiosis may be associated with the physical and emotional well-being of these subjects. Further study of the intestinal microbiota will enable progress in the study of therapeutic approaches of these areas.
Abstract
Anxiety and eating disorders produce a physiological imbalance that triggers alterations in the abundance and composition of gut microbiota. Moreover, the gut-brain axis can be altered by several factors such as diet, lifestyle, infections, and antibiotic treatment. Diet alterations generate gut dysbiosis, which affects immune system responses, inflammation mechanisms, the intestinal permeability, as well as the production of short chain fatty acids and neurotransmitters by gut microbiota, which are essential to the correct function of neurological processes. Recent studies indicated that patients with generalized anxiety or eating disorders (anorexia nervosa, bulimia nervosa, and binge-eating disorders) show a specific profile of gut microbiota, and this imbalance can be partially restored after a single or multi-strain probiotic supplementation. Following the PRISMA methodology, the current review addresses the main microbial signatures observed in patients with generalized anxiety and/or eating disorders as well as the importance of probiotics as a preventive or a therapeutic tool in these pathologies.