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1.
Effect of Lactoferrin Supplementation on Inflammation, Immune Function, and Prevention of Respiratory Tract Infections in Humans: A Systematic Review and Meta-analysis.
Berthon, BS, Williams, LM, Williams, EJ, Wood, LG
Advances in nutrition (Bethesda, Md.). 2022;13(5):1799-1819
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Human and bovine milk contains Lactoferrin, an iron-binding glycoprotein that may modulate immune function and has antimicrobial and antioxidant properties. In this systematic review and meta-analysis, 25 heterogeneous studies were included to evaluate the efficacy of lactoferrin supplementation on systemic inflammation, immune function, and respiratory tract infections in children and adults with various inflammatory conditions. Supplementation with Lactoferrin reduced only a few inflammatory markers, and beneficial effects were observed in less than half of the studies included. However, a beneficial effect was observed when the intervention was continued for at least three months, and dosages, such as 35 mg/d to 833 mg/d in infants, and 400 mg/d to 600 mg/d in adults, were also found to be beneficial. By modulating the immune system, lactoferrin supplementation reduces respiratory tract infections in children and infants. Based on the findings of this study, healthcare professionals may be able to understand the beneficial effects of Lactoferrin supplementation on immune modulation, inflammation reduction, and respiratory tract infections when supplemented as a combination with other supplements or as Lactoferrin alone. However, it is necessary to conduct further robust research to confirm the clinical effectiveness of Lactoferrin supplementation since the current research is limited in number and heterogeneous in nature.
Abstract
Lactoferrin (Lf) is a glycoprotein present in human and bovine milk with antimicrobial and immune-modulating properties. This review aimed to examine the evidence for the effect of Lf supplementation on inflammation, immune function, and respiratory tract infections (RTIs) in humans. Online databases were searched up to December 2020 to identify relevant, English-language articles that examined the effect of Lf supplementation in human subjects of all ages, on either inflammation, immune cell populations or activity, or the incidence, duration, or severity of respiratory illness or RTIs. Twenty-five studies (n = 20 studies in adults) were included, of which 8 of 13 studies (61%) in adults reported a decrease in at least 1 systemic inflammatory biomarker. Immune function improved in 6 of 8 studies (75%) in adults, with changes in immune cell populations in 2 of 6 studies (33%), and changes in immune cell activity in 2 of 5 studies (40%). RTI outcomes were reduced in 6 of 10 studies (60%) (n = 5 in adults, n = 5 in children), with decreased incidence in 3 of 9 studies (33%), and either decreased frequency (2/4, 50%) or duration (3/6, 50%) in 50% of studies. In adults, Lf reduced IL-6 [mean difference (MD): -24.9 pg/mL; 95% CI: -41.64, -8.08 pg/mL], but not C-reactive protein (CRP) [standardized mean difference: -0.09; 95% CI: -0.82, 0.65], or NK cell cytotoxicity [MD: 4.84%; 95% CI: -3.93, 13.60%]. RTI incidence was reduced in infants and children (OR: 0.78; 95% CI: 0.61, 0.98) but not in adults (OR: 1.00; 95% CI: 0.76, 1.32). Clinical studies on Lf supplementation are limited, although findings show 200 mg Lf/d reduces systemic inflammation, while formulas containing 35-833 mg Lf/d may reduce RTI incidence in infants and children, suggesting improved immune function. Future research is required to determine optimal supplementation strategies and populations most likely to benefit from Lf supplementation. This trial was registered at PROSPERO (https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021232186) as CRD42021232186.
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Micronutrients Deficiency, Supplementation and Novel Coronavirus Infections-A Systematic Review and Meta-Analysis.
Wang, MX, Gwee, SXW, Pang, J
Nutrients. 2021;13(5)
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Coronaviruses are a family of enveloped RNA viruses capable of infecting both humans and animals. A robust immune system has general protective effects against disease infection and severity. Micronutrients are shown to be fundamental in strengthening and maintaining immune function. The aim of this study was to systematically assess the associations between micronutrient supplementation or deficiency, with novel coronavirus incidence and its associated severity. This study is a systematic review and meta-analysis of 19 studies. Only literature on COVID-19 induced by SARS-CoV-2 were recovered from the systematic search. Results demonstrate significantly reduced odds of COVID-19 incidence, and ICU admissions or severe/critical disease onset in individuals without micronutrient deficiency. Authors conclude that integrating micronutrients into the prevention and therapeutic management of COVID-19 may complement nonpharmaceutical interventions to reduce the risk of transmission and disease severity in an unvaccinated population.
Abstract
BACKGROUND Micronutrients play roles in strengthening and maintaining immune function, but their supplementation and/or deficiency effects on respiratory tract infections are inconclusive. This review aims to systematically assess the associations between micronutrient supplementation or deficiency, with novel coronavirus incidence and disease severity. METHODS Systematic literature searches conducted in five electronic databases identified 751 unique studies, of which 33 studies (five supplementation studies, one supplementation and deficiency study, and 27 deficiency studies) were eventually included in this review. Proportions of incidence and severity outcomes in each group, and adjusted summary statistics with their relevant 95% confidence intervaIs (CI) were extracted. Data from 19 studies were pooled in meta-analysis using the generic inverse variance method. FINDINGS A total of 360,346 patients across 16 countries, with a mean age between 32 and 87.7 years, were involved across 33 studies. All studies were on COVID-19 infections. In individuals without micronutrient deficiency, there was a significant reduction on odds of COVID-19 incidence (pooled OR: 0.37, 95% CI: 0.18, 0.78), and ICU admissions or severe/critical disease onset when combined as a severity outcome (pooled OR: 0.26, 95% CI: 0.08, 0.89). Insignificant protective effects were observed on other outcome measures, namely mortality, ICU admission, progression to respiratory-related complications, severe/critical disease onset or requiring respiratory support and hospitalization rate. CONCLUSION The absence of micronutrient deficiency significantly reduced COVID-19 incidence and clinical deterioration in hospitalized patients. Usage of micronutrients as prophylaxis and complementary supplement in therapeutic management of COVID-19 patients may be a promising and cost-effective approach warranting in-depth investigation.
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COVID-19: The Inflammation Link and the Role of Nutrition in Potential Mitigation.
Zabetakis, I, Lordan, R, Norton, C, Tsoupras, A
Nutrients. 2020;12(5)
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By May 2020, the novel coronoavirus COVID-19 had infected over 4 million people worldwide. Spread through droplet, it gains entry to body cells through ACE2 cell receptors, causing viral infection-related inflammation, and predominantly infects the lower respiratory tract. Those with non-communicable diseases with COVID-19 experience increased inflammation and have a higher risk of adverse outcomes and mortality. This review article gives details of the mechanisms involved in a cytokine storm (an uncontrolled inflammatory response) and current treatment options, before discussing the immune-balancing and anti-inflammatory potential of healthy nutrition in reducing susceptibility to developing infections. Nutrition Practitioners looking to support the immunity and inflammation of their clients will find the summary research presented in relation to dietary strategies, different food groups and nutrients a useful basis for further study.
Abstract
The novel coronavirus disease (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has engulfed the world, affecting more than 180 countries. As a result, there has been considerable economic distress globally and a significant loss of life. Sadly, the vulnerable and immunocompromised in our societies seem to be more susceptible to severe COVID-19 complications. Global public health bodies and governments have ignited strategies and issued advisories on various handwashing and hygiene guidelines, social distancing strategies, and, in the most extreme cases, some countries have adopted "stay in place" or lockdown protocols to prevent COVID-19 spread. Notably, there are several significant risk factors for severe COVID-19 infection. These include the presence of poor nutritional status and pre-existing noncommunicable diseases (NCDs) such as diabetes mellitus, chronic lung diseases, cardiovascular diseases (CVD), obesity, and various other diseases that render the patient immunocompromised. These diseases are characterized by systemic inflammation, which may be a common feature of these NCDs, affecting patient outcomes against COVID-19. In this review, we discuss some of the anti-inflammatory therapies that are currently under investigation intended to dampen the cytokine storm of severe COVID-19 infections. Furthermore, nutritional status and the role of diet and lifestyle is considered, as it is known to affect patient outcomes in other severe infections and may play a role in COVID-19 infection. This review speculates the importance of nutrition as a mitigation strategy to support immune function amid the COVID-19 pandemic, identifying food groups and key nutrients of importance that may affect the outcomes of respiratory infections.
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The role of vitamin D in the prevention of coronavirus disease 2019 infection and mortality.
Ilie, PC, Stefanescu, S, Smith, L
Aging clinical and experimental research. 2020;32(7):1195-1198
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The World Health Organisation declared COVID-19 caused by the virus SARS-CoV-2 a global pandemic. ACE-2 is the host cell receptor responsible for mediating infection by SARS-CoV-2. The main aim of this study was to assess the association between the mean levels of vitamin D in various countries and the mortality caused by COVID-19. A secondary aim was to identify any association/s between the mean vitamin D levels in various countries and the number of cases of COVID-19. This study is a cross-sectional analysis of based on studies carried out on European countries. Results indicate a potential crude association between the mean vitamin D levels in various European countries with COVID-19 cases and COVID-19 mortality. Authors conclude that further studies about vitamin D levels in COVID-19 patients with different degrees of disease severity should be performed.
Abstract
WHO declared SARS-CoV-2 a global pandemic. The present aim was to propose an hypothesis that there is a potential association between mean levels of vitamin D in various countries with cases and mortality caused by COVID-19. The mean levels of vitamin D for 20 European countries and morbidity and mortality caused by COVID-19 were acquired. Negative correlations between mean levels of vitamin D (average 56 mmol/L, STDEV 10.61) in each country and the number of COVID-19 cases/1 M (mean 295.95, STDEV 298.7, and mortality/1 M (mean 5.96, STDEV 15.13) were observed. Vitamin D levels are severely low in the aging population especially in Spain, Italy and Switzerland. This is also the most vulnerable group of the population in relation to COVID-19. It should be advisable to perform dedicated studies about vitamin D levels in COVID-19 patients with different degrees of disease severity.
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The impact of nutrition on COVID-19 susceptibility and long-term consequences.
Butler, MJ, Barrientos, RM
Brain, behavior, and immunity. 2020;87:53-54
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The impacts of Covid-19 are being felt across the world, affecting health, healthcare and economies. Statistics from across the world are showing that the elderly, those with underlying medical conditions and under-represented minority groups are particularly vulnerable to severe complications and have a higher risk of dying of Covid-19. This opinion piece presents arguments for the importance of focusing on diet to support health resilience in general and the immune system in particular, to minimise the impact of this and future viruses. Research is presented on excessive intake of saturated fat leading to chronic activation of the innate immune system (first line, rapid defence against infection), resulting in inflammation, and associated heightened susceptibility to complications of viral infection. The standard western diet (high saturated fat, refined carbohydrates and sugars, low levels of fibre, unsaturated fat and antioxidants) has also been shown to affect the adaptive immune system (second line, delayed defence against infection), depressing its action against infection. The piece also discusses possible long-term, future impacts of those recovered from Covid-19 infection, particularly in relation to neurodegenerative diseases such as Alzheimer’s. The authors call for fresh, healthy wholefoods to be readily available and affordable to everyone in society.
Abstract
While all groups are affected by the COVID-19 pandemic, the elderly, underrepresented minorities, and those with underlying medical conditions are at the greatest risk. The high rate of consumption of diets high in saturated fats, sugars, and refined carbohydrates (collectively called Western diet, WD) worldwide, contribute to the prevalence of obesity and type 2 diabetes, and could place these populations at an increased risk for severe COVID-19 pathology and mortality. WD consumption activates the innate immune system and impairs adaptive immunity, leading to chronic inflammation and impaired host defense against viruses. Furthermore, peripheral inflammation caused by COVID-19 may have long-term consequences in those that recover, leading to chronic medical conditions such as dementia and neurodegenerative disease, likely through neuroinflammatory mechanisms that can be compounded by an unhealthy diet. Thus, now more than ever, wider access to healthy foods should be a top priority and individuals should be mindful of healthy eating habits to reduce susceptibility to and long-term complications from COVID-19.
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Danger signals and inflammaging in osteoarthritis.
Millerand, M, Berenbaum, F, Jacques, C
Clinical and experimental rheumatology. 2019;37 Suppl 120(5):48-56
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Osteoarthritis (OA) is the most common and disabling joint disease worldwide and aging is the most important risk factor for its development. It was considered a ‘wear and tear’ disease for a long time, however it is now clear that low-grade inflammation is at the root of OA. This process is called ‘inflammaging’ – the presence of low-grade inflammation and decreased efficiency of the immune system with aging. This highly technical review paper describes the reaction of the immune system to small molecules that begin to circulate after cell stress or damage in the joints (known as damage-associated molecular patterns or DAMPs), causing inflammation. The paper includes a discussion on potential medication targets, including anti-inflammatory compounds such as ginger. Nutrition Practitioners working with OA and wanting to understand the inflammatory process involved will find this paper useful.
Abstract
Osteoarthritis (OA) is the most common age-related chronic and disabling joint disease. Long considered to be a "wear and tear" disease, OA is now seen as a low-grade inflammation disease that affects all tissues of the joint, involving cartilage degradation, bone remodelling, osteophytes, and synovitis. The process, called inflammaging, is characterised by the association of low-grade inflammation, profound changes in intra-cellular mechanisms, and the decreased efficiency of the immune system with ageing. The activation of innate immunity plays a critical role in the development and progression of OA. Innate immunity, including inflammasome activation, is triggered by small endogenous molecules called alarmins or damage-associated molecular patterns (DAMPs). These molecules are released in the extracellular media after cell stress or damage, bind to pathogen-recognition receptors (PRRs), such as Toll-like receptors (TLRs) and the receptor for advanced glycation end products (RAGE), and activate the secretion of pro-inflammatory factors, leading to joint inflammation. Moreover, such sterile inflammation triggers cell senescence, characterised by a senescence-associated secretory phenotype (SASP). Understanding the substantial age-related changes of joint tissues that influence the pathogenesis of OA is critical to improving the quality of life of elderly people in the context of increased life expectancy. This review will focus on age-related sterile inflammation in OA and highlight the various innovative and promising therapies targeting the mechanisms of aging.
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Serological investigation of IgG and IgE antibodies against food antigens in patients with inflammatory bowel disease.
Wang, HY, Li, Y, Li, JJ, Jiao, CH, Zhao, XJ, Li, XT, Lu, MJ, Mao, XQ, Zhang, HJ
World journal of clinical cases. 2019;7(16):2189-2203
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Crohn's disease and ulcerative colitis are relapsing gut inflammatory diseases that are usually referred to as Inflammatory Bowel Disease (IBD). It may be triggered by an imbalance in immune response in response to environmental factors such as diet. The aim of this retrospective study was to evaluate the presence of IgG and IgE mediated antibodies to food antigens in IBD patients. There were one hundred and thirty-seven IBD patients participating in this study, including forty Ulcerative colitis patients and ninety-seven Crohn's disease patients against fifty healthy controls to test serum IgG antibodies to fourteen specific food antigens and serum IgE antibodies to fourteen specific food antigens. There were significantly higher IgG antibodies in response to food antigens in Crohn's disease patients than in Ulcerative colitis patients and healthy controls. Food antigens such as tomato, corn, egg, rice, and soybean exhibited varying levels of IgG antibody responses in Crohn's disease patients and ulcerative colitis patients. Smokers were more likely to develop IgG reactions. Further robust research is needed to examine more IgG-specific food antigens to help manage IBD with an elimination rotation diet. The results of this study can help healthcare professionals understand the importance of diagnosing food intolerances when treating IBD.
Abstract
BACKGROUND Food antigens have been shown to participate in the etiopathogenesis of inflammatory bowel disease (IBD), but their clinical value in IBD is still unclear. AIM: To analyze the levels of specific immunoglobulin G (IgG) and E (IgE) antibodies against food antigens in IBD patients and to determine their clinical value in the pathogenesis of IBD. METHODS We performed a retrospective study based on patients who visited the First Affiliated Hospital of Nanjing Medical University between August 2016 and January 2018. A total of 137 IBD patients, including 40 patients with ulcerative colitis (UC) and 97 patients with Crohn's disease (CD), and 50 healthy controls (HCs), were recruited. Serum food-specific IgG antibodies were detected by semi-quantitative enzyme-linked immunosorbent assay, and serum food-specific IgE antibodies were measured by Western blot. The value of food-specific IgG antibodies was compared among different groups, and potent factors related to these antibodies were explored by binary logistic regression. RESULTS Food-specific IgG antibodies were detected in 57.5% of UC patients, in 90.72% of CD patients and in 42% of HCs. A significantly high prevalence and titer of food-specific IgG antibodies were observed in CD patients compared to UC patients and HCs. The number of IgG-positive foods was greater in CD and UC patients than in HCs (CD vs HCs, P = 0.000; UC vs HCs, P = 0.029). The top five food antigens that caused positive specific IgG antibodies in CD patients were tomato (80.68%), corn (69.32%), egg (63.64%), rice (61.36%), and soybean (46.59%). The foods that caused positive specific IgG antibodies in UC patients were egg (60.87%), corn (47.83%), tomato (47.83%), rice (26.09%), and soybean (21.74%). Significantly higher levels of total food-specific IgG were detected in IBD patients treated with anti-TNFα therapy compared to patients receiving steroids and immunosuppressants (anti-TNFα vs steroids, P = 0.000; anti-TNFα vs immunosuppressants, P = 0.000; anti-TNFα vs steroids + immunosuppressants, P = 0.003). A decrease in food-specific IgG levels was detected in IBD patients after receiving anti-TNFα therapy (P = 0.007). Patients who smoked and CD patients were prone to developing serum food-specific IgG antibodies [Smoke: OR (95%CI): 17.6 (1.91-162.26), P = 0.011; CD patients: OR (95%CI): 12.48 (3.45-45.09), P = 0.000]. There was no difference in the prevalence of food-specific IgE antibodies among CD patients (57.1%), UC patients (65.2%) and HCs (60%) (P = 0.831). CONCLUSION CD patients have a higher prevalence of food-specific IgG antibodies than UC patients and HCs. IBD patients are prone to rice, corn, tomato and soybean intolerance. Smoking may be a risk factor in the occurrence of food-specific IgG antibodies. Food-specific IgG antibodies may be a potential method in the diagnosis and management of food intolerance in IBD.
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The Role of Dietary Fiber in Rheumatoid Arthritis Patients: A Feasibility Study.
Häger, J, Bang, H, Hagen, M, Frech, M, Träger, P, Sokolova, MV, Steffen, U, Tascilar, K, Sarter, K, Schett, G, et al
Nutrients. 2019;11(10)
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Rheumatoid arthritis (RA) is a chronic, autoimmune inflammatory musculoskeletal disorder, affecting around 1% of the world population. Risk factors are genetic and environmental, with diet appearing to be an important environmental trigger. The impacts of diet on the gut microbiota are well studied, including the ability of the gut microbiome to manipulate the immune system. This small feasibility study of 36 patients with RA aimed to examine the effect of short-term high fibre dietary supplementation on T-reg cell numbers (cells which regulate the immune system). A high fibre bar was provided to study subjects for 28 days and measurements taken of immune and inflammation markers, bone erosion, gut bacterial changes and quality of life. The authors found a positive improvement to patient immune systems at the end of the intervention, as well as decreased markers of bone erosion. Physical functioning and quality of life were also reported as significantly improved. Whilst this is a small uncontrolled trial, the results support increasing the fibre intake when working with RA clients.
Abstract
Short-chain fatty acids are microbial metabolites that have been shown to be key regulators of the gut-joint axis in animal models. In humans, microbial dysbiosis was observed in rheumatoid arthritis (RA) patients as well as in those at-risk to develop RA, and is thought to be an environmental trigger for the development of clinical disease. At the same time, diet has a proven impact on maintaining intestinal microbial homeostasis. Given this association, we performed a feasibility study in RA patients using high-fiber dietary supplementation with the objective to restore microbial homeostasis and promote the secretion of beneficial immunomodulatory microbial metabolites. RA patients (n = 36) under routine care received daily high-fiber bars or cereals for 28 days. Clinical assessments and laboratory analysis of immune parameters in blood and stool samples from RA patients were done before and after the high-fiber dietary supplementation. We observed an increase in circulating regulatory T cell numbers, favorable Th1/Th17 ratios, as well as decreased markers of bone erosion in RA patients after 28 days of dietary intervention. Furthermore, patient-related outcomes of RA improved. Based on these results, we conclude that controlled clinical studies of high-fiber dietary interventions could be a viable approach to supplement or complement current pharmacological treatment strategies.
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Assessment of sleep and obesity in adults and children: Observational study.
Bonanno, L, Metro, D, Papa, M, Finzi, G, Maviglia, A, Sottile, F, Corallo, F, Manasseri, L
Medicine. 2019;98(46):e17642
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Sleep is essential to support the functions and health of the entire body. The aim of this study was to investigate the association between sleep duration and quality, and overweight risk and obesity in children and adults. The study was conducted on secondary school children. It involved 199 subjects of which 71 were adults (29 males and 42 females) with age between 29 and 65 years, and 128 children (73 males and 55 females) with age between 10 and 13 years. Results indicate that the duration and quality of sleep can represent a risk factor of overweight and obesity in examined subjects (both adults and children irrespective of their gender). Authors conclude that sufficient sleep is required to maintain a normal weight.
Abstract
The sleep allows many psychological processes, such as immune system activity, body metabolism and hormonal balance, emotional and mental health, learning, mnemonic processes. The lack of sleep could undermine mental and physical purposes, causing an alteration in cognitive functions or metabolic disorders. In our study, we have examined the irregular sleep effects with the overweight and obesity risk in children and adults.The sample was composed of 199 subjects, of which 71 adults, (29 males and 42 females), and 128 children (73 males and 55 females). We have measured the weight and height with standard techniques; we also have measured the body mass index dividing the weight in kg with the height square expressed in meters (kg/m). Subjects were divided into underweight, normal weight, overweight, and obese. Were administered some questionnaires to measure the quantity and quality of sleep, and eating habits and individual consumption of food.Analysis of demographic variables not showed significant differences between male and female groups but highlighted a significant trend differences in normal-weight score. The clinical condition has a substantial impact on body mass index score and sleep hours were significant predictor on this.Quantity and quality sleep can also represent a risk factor of overweight and obesity, so sufficient sleep is a factor that influence a normal weight. Adults and children that sleep less, have an increase in obesity and overweight risk with dysfunctional eating behaviors, decreased physical activity, and metabolic changes.
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The Dynamic Interplay between the Gut Microbiota and Autoimmune Diseases.
Xu, H, Liu, M, Cao, J, Li, X, Fan, D, Xia, Y, Lu, X, Li, J, Ju, D, Zhao, H
Journal of immunology research. 2019;2019:7546047
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The human gut, or intestines, are populated with commensal bacteria which live in harmony with us and support various biological functions. The main role of the gut microbiota is to maintain the homeostasis of our immune system. It does this by maintaining the integrity of the intestinal lining and helping with digestive processes, production, and absorption of nutrients, and harvesting of immune cells. Our gut microbiome develops throughout infancy and confers benefits in adulthood and so any disruption to its development may impact on health. An imbalance between these helpful bacteria and more harmful pathogenic bacteria, which are also present in smaller amounts, is called dysbiosis and is a common factor in many autoimmune conditions. Autoimmune conditions are characterised by an over-active immune system where immune cells attack our own body. Imbalances in gut microbiota are also common, and diet is thought to be a key factor alongside other genetic and environmental factors. Evidence suggests that long-term dysbiosis may trigger autoimmune disease, amplify disease progression or both, as seen in studies on Arthritis, Lupus, Inflammatory bowel disease. The gut microbiota can be partially restored and supported with antimicrobial interventions, prebiotics, and selective probiotics. The review concludes that therapies targeting the gut microbiota may be effective in the future prevention or treatment of autoimmune diseases.
Abstract
The human gut-resident commensal microbiota is a unique ecosystem associated with various bodily functions, especially immunity. Gut microbiota dysbiosis plays a crucial role in autoimmune disease pathogenesis as well as in bowel-related diseases. However, the role of the gut microbiota, which causes or influences systemic immunity in autoimmune diseases, remains elusive. Aryl hydrocarbon receptor, a ligand-activated transcription factor, is a master moderator of host-microbiota interactions because it shapes the immune system and impacts host metabolism. In addition, treatment optimization while minimizing potential adverse effects in autoimmune diseases remains essential, and modulation of the gut microbiota constitutes a potential clinical therapy. Here, we present evidence linking gut microbiota dysbiosis with autoimmune mechanisms involved in disease development to identify future effective approaches based on the gut microbiota for preventing autoimmune diseases.