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The Influence of n-3PUFA Supplementation on Muscle Strength, Mass, and Function: A Systematic Review and Meta-Analysis.
Santo André, HC, Esteves, GP, Barreto, GHC, Longhini, F, Dolan, E, Benatti, FB
Advances in nutrition (Bethesda, Md.). 2023;14(1):115-127
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Omega 3 polyunsaturated fatty acids (n-3PUFA) are long-chain polyunsaturated fatty acids essential to human health. They play a role in cell membrane integrity, immune and inflammation regulation, cognition and neuromuscular function. As the human body cannot make these fatty acids, they need to be obtained through diet or supplementation. Regarding skeletal muscle, recent research showed that n-3PUFAs may increase the uptake of amino acids by increasing the membrane fluidity in the muscle, and by activating pathways that inhibit protein breakdown. This led to the hypothesis that n-3PUFAs may enhance muscle mass gain and strength. This systematic review sought to gather all available evidence about the impact of n-3PUFA supplementation on muscle mass, strength, and function in healthy young and older adults. The review included 14 studies with a total of 1443 participants. The authors found that n-3PUFA supplementation had no significant effect on muscle mass or muscle function in healthy young and older adults, however, a very small but significant positive effect was noted regarding muscle strength. In the discussion section, the authors explain the challenges of their review and how these findings integrate with the current understanding and other research findings. They concluded more research is needed to get a better insight into the effects of n-3PUFA on muscle function and the variants.
Abstract
The effects of omega 3 polyunsaturated fatty acids (n-3PUFA) supplementation on skeletal muscle are currently unclear. The purpose of this systematic review was to synthesize all available evidence regarding the influence of n-3PUFA supplementation on muscle mass, strength, and function in healthy young and older adults. Four databases were searched (Medline, Embase, Cochrane CENTRAL, and SportDiscus). Predefined eligibility criteria were determined according to Population, Intervention, Comparator, Outcomes, and Study Design. Only peer-reviewed studies were included. The Cochrane RoB2 Tool and the NutriGrade approach were used to access risk of bias and certainty in evidence. Effect sizes were calculated using pre-post scores and analyzed using a three-level, random-effects meta-analysis. When sufficient studies were available, subanalyses were performed in the muscle mass, strength, and function outcomes according to participant's age (<60 or ≥60 years), supplementation dosage (<2 or ≥2 g/day), and training intervention ("resistance training" vs. "none or other"). Overall, 14 individual studies were included, total 1443 participants (913 females; 520 males) and 52 outcomes measures. Studies had high overall risk of bias and consideration of all NutriGrade elements resulted in a certainty assessment of moderate meta-evidence for all outcomes. n-3PUFA supplementation had no significant effect on muscle mass (standard mean difference [SMD] = 0.07 [95% CI: -0.02, 0.17], P = 0.11) and muscle function (SMD = 0.03 [95% CI: -0.09, 0.15], P = 0.58), but it showed a very small albeit significant positive effect on muscle strength (SMD = 0.12 [95% CI: 0.006, 0.24], P = 0.04) in participants when compared with placebo. Subgroup analyses showed that age, supplementation dose, or cosupplementation alongside resistance training did not influence these responses. In conclusion, our analyses indicated that n-3PUFA supplementation may lead to very small increases in muscle strength but did not impact muscle mass and function in healthy young and older adults. To our knowledge, this is the first review and meta-analysis investigating whether n-3PUFA supplementation can lead to increases in muscle strength, mass, and function in healthy adults. Registered protocol: doi.org/10.17605/OSF.IO/2FWQT.
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An Open-Label Case Series of Glutathione Use for Symptomatic Management in Children with Autism Spectrum Disorder.
Radwan, K, Wu, G, Banks-Word, K, Rosenberger, R
Medical sciences (Basel, Switzerland). 2023;11(4)
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Autism spectrum disorder (ASD) is a neurodevelopmental disorder that can cause impaired social–emotional interactions, impaired language and communication skills, repetitive or restrictive behaviours, and sometimes aggressive behaviour. The causes of ASD are complex and unclear. There is an increasing recognition that ASD might be associated with oxidative stress and the toxic build-up of reactive oxygen species (ROS). Glutathione acts as an antioxidant, a free radical scavenger and a detoxifying agent. The aim of this 12-week open-label pilot study was to investigate the tolerability and effectiveness of oral supplementation with OpitacTM glutathione as a treatment for patients with ASD. Six participants took part. Glutathione was generally well-tolerated except in the case of one subject. Some subjects showed improved total antioxidant capacity, and there was a mild improvement in the severity of ASD symptoms in 66.7% of the patients. However, none of the observed changes in the pre- and post-treatment oxidative laboratory markers and Aberrant Behaviour Checklist (ABC) scores were statistically significant. An imbalance in redox reactions is only one of the many factors contributing to ASD. Further studies are necessary to investigate the other factors.
Abstract
Autism spectrum disorder (ASD) is a type of neurodevelopmental disorder that has been diagnosed in an increasing number of children around the world. The existing data suggest that early diagnosis and intervention can improve ASD outcomes. The causes of ASD remain complex and unclear, and there are currently no clinical biomarkers for autism spectrum disorder. There is an increasing recognition that ASD might be associated with oxidative stress through several mechanisms including abnormal metabolism (lipid peroxidation) and the toxic buildup of reactive oxygen species (ROS). Glutathione acts as an antioxidant, a free radical scavenger and a detoxifying agent. This open-label pilot study investigates the tolerability and effectiveness of oral supplementation with OpitacTM gluthathione as a treatment for patients with ASD. The various aspects of glutathione OpitacTM glutathione bioavailability were examined when administered by oral routes. The absorption of glutathione from the gastrointestinal tract has been recently investigated. The results of this case series suggest that oral glutathione supplementation may improve oxidative markers, but this does not necessarily translate to the observed clinical improvement of subjects with ASD. The study reports a good safety profile of glutathione use, with stomach upset reported in four out of six subjects. This article discusses the role of the gut microbiome and redox balance in ASD and notes that a high baseline oxidative burden may make some patients poor responders to glutathione supplementation. In conclusion, an imbalance in redox reactions is only one of the many factors contributing to ASD, and further studies are necessary to investigate other factors, such as impaired neurotransmission, immune dysregulation in the brain, and mitochondrial dysfunction.
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Exploring choices of early nutritional support for patients with sepsis based on changes in intestinal microecology.
Yang, XJ, Wang, XH, Yang, MY, Ren, HY, Chen, H, Zhang, XY, Liu, QF, Yang, G, Yang, Y, Yang, XJ
World journal of gastroenterology. 2023;29(13):2034-2049
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Sepsis is a condition brought about by infection and results in organ dysfunction and gut microbiota imbalance. Nutrition plays a large part in recovery from sepsis, however it is unclear as to the optimal diet for gut microbial balance in individuals with sepsis. This randomised control trial of 30 individuals with sepsis aimed to determine the optimal delivery of nutrition for gut microbial health either through a gastric tube (TEN), through the jugular vein (TPN), or a mixture of the two modes (SPN). The results showed differences in gut microbiota composition between the different modes of nutrition. Enterococcus increased in TEN, Campylobacter decreased in TPN, and Dialister decreased in SPN groups. Fermentation products produced by gut microbiota also changed depending on the mode of nutrition, with the TEN group showing improvements amongst the most fermentation products. Individuals in the TEN group also showed improved immune system function alongside those in the SPN group. It was concluded that based upon improvements to the immune system and gut microbiota, TEN is the most suitable mode for nutrition in individuals with sepsis. This study could be used by healthcare professionals to understand that nutrition methods for individuals with sepsis aren’t equally effective and recovery may be faster if individuals receive nutrition through a gastric tube.
Abstract
BACKGROUND Sepsis exacerbates intestinal microecological disorders leading to poor prognosis. Proper modalities of nutritional support can improve nutrition, immunity, and intestinal microecology. AIM: To identify the optimal modality of early nutritional support for patients with sepsis from the perspective of intestinal microecology. METHODS Thirty patients with sepsis admitted to the intensive care unit of the General Hospital of Ningxia Medical University, China, between 2019 and 2021 with indications for nutritional support, were randomly assigned to one of three different modalities of nutritional support for a total of 5 d: Total enteral nutrition (TEN group), total parenteral nutrition (TPN group), and supplemental parenteral nutrition (SPN group). Blood and stool specimens were collected before and after nutritional support, and changes in gut microbiota, short-chain fatty acids (SCFAs), and immune and nutritional indicators were detected and compared among the three groups. RESULTS In comparison with before nutritional support, the three groups after nutritional support presented: (1) Differences in the gut bacteria (Enterococcus increased in the TEN group, Campylobacter decreased in the TPN group, and Dialister decreased in the SPN group; all P < 0.05); (2) different trends in SCFAs (the TEN group showed improvement except for Caproic acid, the TPN group showed improvement only for acetic and propionic acid, and the SPN group showed a decreasing trend); (3) significant improvement of the nutritional and immunological indicators in the TEN and SPN groups, while only immunoglobulin G improved in the TPN group (all P < 0.05); and (4) a significant correlation was found between the gut bacteria, SCFAs, and nutritional and immunological indicators (all P < 0.05). CONCLUSION TEN is recommended as the preferred mode of early nutritional support in sepsis based on clinical nutritional and immunological indicators, as well as changes in intestinal microecology.
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Impact of Blueberry Consumption on the Human Fecal Bileacidome: A Pilot Study of Bile Acid Modulation by Freeze-Dried Blueberry.
Gagnon, W, Garneau, V, Trottier, J, Verreault, M, Couillard, C, Roy, D, Marette, A, Drouin-Chartier, JP, Vohl, MC, Barbier, O
Nutrients. 2022;14(18)
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Primary bile acids (BAs) are made in the liver from cholesterol. They are released into the small intestine, where they aid fat digestion and absorption. Most BAs are reabsorbed from the gut, yet a small amount gets modified by the gut bacteria, forming secondary BAs destined for faecal excretion. Excess secondary BAs have negative health consequences. The different types of primary BAs influence many physiological functions. Such as glucose regulation, fat metabolism and absorption, intestinal inflammation and immunity, as well as gut bacteria diversity. For optimal BA metabolism, they are tightly regulated by the body, as minimal changes in BA pool and composition can have a significant impact on overall health. The composition of the BA pool can be influenced by gut bacteria, metabolic disorders, pathologies of the liver and gut, and diet. Dietary polyphenols, a plant-based compound, have been of particular interest here. This study sought to investigate the impact of supplementary freeze-dried blueberry powder (BBP), a rich polyphenol source, on the faecal BA pool composition in people at risk of metabolic syndrome. For this 11 men and 13 women were supplemented for 8 weeks. When compared to the data before the intervention, no significant changes in total BAs were observed. However, the composition of the BA pool changed leading to the accumulation of particular BAs and a reduction in secondary BA levels. This suggested that the consumption of blueberries can be considered a potential clinical intervention to aid the elimination of toxic secondary BAs. As the mechanisms leading to such modifications and their consequences for human health are complex, the authors advocate for investigation in larger population groups and also alert that such changes may be subject to interindividual variability and health status.
Abstract
Cholesterol-derived bile acids (BAs) affect numerous physiological functions such as glucose homeostasis, lipid metabolism and absorption, intestinal inflammation and immunity, as well as intestinal microbiota diversity. Diet influences the composition of the BA pool. In the present study, we analyzed the impact of a dietary supplementation with a freeze-dried blueberry powder (BBP) on the fecal BA pool composition. The diet of 11 men and 13 women at risk of metabolic syndrome was supplemented with 50 g/day of BBP for 8 weeks, and feces were harvested before (pre) and after (post) BBP consumption. BAs were profiled using liquid chromatography coupled with tandem mass spectrometry. No significant changes in total BAs were detected when comparing pre- vs. post-BBP consumption samples. However, post-BBP consumption samples exhibited significant accumulations of glycine-conjugated BAs (p = 0.04), glycochenodeoxycholic (p = 0.01), and glycoursodeoxycholic (p = 0.01) acids, as well as a significant reduction (p = 0.03) in the secondary BA levels compared with pre-BBP feces. In conclusion, the fecal bileacidome is significantly altered after the consumption of BBP for 8 weeks. While additional studies are needed to fully understand the underlying mechanisms and physiological implications of these changes, our data suggest that the consumption of blueberries can modulate toxic BA elimination.
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Western Dietary Pattern Antioxidant Intakes and Oxidative Stress: Importance During the SARS-CoV-2/COVID-19 Pandemic.
Trujillo-Mayol, I, Guerra-Valle, M, Casas-Forero, N, Sobral, MMC, Viegas, O, Alarcón-Enos, J, Ferreira, IM, Pinho, O
Advances in nutrition (Bethesda, Md.). 2021;12(3):670-681
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The Atlantic diet (AD), Mediterranean diet (MD) and diets which follow the American dietary guidelines (AmD) all supply enough nutrients for the body to stay healthy. However, during periods of viral pandemics, such as the Covid-19 pandemic, these diets may be inadequate for optimal resistance to infection. Furthermore, nutrient requirements may alter with age, stress, and health. This review paper aimed to discuss the three different diets and their suitability depending on age and physical and mental state. Supplementation during a pandemic was also discussed. When the body contracts viruses such as Covid-19, reactive oxygen species can accumulate resulting in oxidative stress which can damage the cells. Nutrients in the diet, which act as antioxidants may be of benefit, in this instance, however traditional balanced diets such as the AD, MD and AmD may be inadequate. In tandem with a balanced diet, supplementation may improve health. Zinc, vitamin A, selenium, vitamin D, vitamin C, and iron have been shown in research to improve the body’s response to viruses. It was concluded that the Covid-19 pandemic has caused severe infections, which can result in oxidative stress, increasing vulnerability to viral infections. Supplementing certain nutrients may be of benefit especially in vulnerable individuals. This study could be used by healthcare professionals to understand that a balanced diet is essential during viral pandemics, and it may be necessary to consider supplementation for high-risk individuals.
Abstract
The importance of balanced dietary habits, which include appropriate amounts of antioxidants to maintain the immune system, has become increasingly relevant during the current SARS-CoV-2/COVID-19 pandemic, because viral infections are characterized by high oxidative stress. Furthermore, the measures taken by governments to control the pandemic have led to increased anxiety, stress, and depression, which affect physical and mental health, all of which are influenced by nutritional status, diet, and lifestyle. The Mediterranean diet (MD), Atlantic diet (AD), and the Dietary Guidelines for Americans all provide the essential vitamins, minerals, and phenolic compounds needed to activate enzymatic and nonenzymatic antioxidant responses. However, viral pandemics such as the current COVID-19 crisis entail high oxidative damage caused by both the infection and the resultant social stresses within populations, which increases the probability and severity of infection. Balanced dietary patterns such as the MD and the AD are characterized by the consumption of fruit, vegetables, legumes, olive oil, and whole grains with low intakes of processed foods and red meat. For a healthy lifestyle in young adults, the MD in particular provides the required amount of antioxidants per day for vitamins D (0.3-3.8 μg), E (17.0 mg), C (137.2-269.8 mg), A (1273.3 μg), B-12 (1.5-2.0 μg), and folate (455.1-561.3 μg), the minerals Se (120.0 μg), Zn (11.0 mg), Fe (15.0-18.8 mg), and Mn (5.2-12.5 mg), and polyphenols (1171.00 mg) needed to maintain an active immune response. However, all of these diets are deficient in the recommended amount of vitamin D (20 μg/d). Therefore, vulnerable populations such as elders and obese individuals could benefit from antioxidant supplementation to improve their antioxidant response. Although evidence remains scarce, there is some indication that a healthy diet, along with supplemental antioxidant intake, is beneficial to COVID-19 patients.
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Dissecting the interaction between COVID-19 and diabetes mellitus.
Chee, YJ, Tan, SK, Yeoh, E
Journal of diabetes investigation. 2020;11(5):1104-1114
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Several countries have reported higher death rates and more severe cases of covid-19 amongst individuals with chronic diseases such as type 2 diabetes. This review of 100 papers aimed to investigate the interconnecting factors which may contribute to poorer prognosis in individuals with covid-19 and type 2 diabetes. Although the evidence suggests that patients with type 2 diabetes have poorer outcomes after contracting covid-19, they are not more susceptible to infection. The paper reported that mechanisms which may increase severity in type 2 diabetics are abnormal immune function, increased susceptibility to inflammation, the increased adherence of the virus to target cells and reduced ability to fight infection. It is important to manage blood sugars when suffering from covid-19. The paper reviewed the use of several medications such as metformin, dipeptidyl peptidase-4 inhibitors (DPP4), glucagon-like peptide-1 agonists and insulin in the context of individuals suffering from covid-19, with insulin being the treatment of choice in the acutely ill patient. Current treatments of covid-19 were also reviewed such as chloroquine and hydroxychloroquine, Lopinavir-ritonavir, IL-6 receptor agonists, type 1 interferon and remdesivir. It was concluded that clinicians should be aware of the risks in patients with type 2 diabetes and covid-19. However as new data is made available, the chronic and long-term implications will become clearer. This study could be used by health care professionals to ensure that patients with type 2 diabetes do everything they can to avoid covid-19 infection and that if contracted these patients are closely monitored for severe disease.
Abstract
Coronavirus disease 2019 (COVID-19) is a global pandemic that is caused by a novel coronavirus, severe acute respiratory syndrome coronavirus-2. Data from several countries have shown higher morbidity and mortality among individuals with chronic metabolic diseases, such as diabetes mellitus. In this review, we explore the contributing factors for poorer prognosis in these individuals. As a significant proportion of patients with COVID-19 also have diabetes mellitus, this adds another layer of complexity to their management. We explore potential interactions between antidiabetic medications and renin-angiotensin-aldosterone system inhibitors with COVID-19. Suggested recommendations for the use of antidiabetic medications for COVID-19 patients with diabetes mellitus are provided. We also review pertinent clinical considerations in the management of diabetic ketoacidosis in COVID-19 patients. In addition, we aim to increase clinicians' awareness of the metabolic effects of promising drug therapies for COVID-19. Finally, we highlight the importance of timely vaccinations for patients with diabetes mellitus.
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The Long Haul of COVID-19 Recovery: Immune Rejuvenation versus Immune Support.
Bland, JS
Integrative medicine (Encinitas, Calif.). 2020;19(6):18-22
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Following Covid-19 infection, sufferers have reported various residual symptoms, which have been likened to those experienced by chronic fatigue sufferers and those with Gulf War syndrome. This review paper aimed to assess whether the body has a similar immune response to these diseases during Covid-19, and if so, what therapies could be used. It also reviewed any diet and lifestyle factors that may be affecting the immune response. The paper stated that Covid-19 infection is associated with inflammation, which can damage immune cells and inflammation prior to Covid-19 infection may contribute to severity of the infection. Prior research in seemingly healthy individuals indicates that environment, diet, and lifestyle factors can all contribute to differing “immune identities” and eliminating immune cells which carry the imprint of memories should be a therapy focus in Covid-19 patients. Fasting, diets low in refined sugars and high in omega-3 and plant chemicals were discussed as ways for the body to clear out immune cells. It was concluded that personalising therapy strategies based on an individual’s immune identity to reduce inflammation could ultimately support the immune system. This paper could be used by healthcare professionals to understand the importance of diet and lifestyle changes to reduce inflammation and support the immune system.
Abstract
With the COVID-19 pandemic still affecting communities all over the world and "Long Haul" chronic health issues emerging, it is time for us to look back at past multi-symptom health conditions that required a different approach to their treatment, beyond just managing symptoms. It is important for us to consider how to apply what we have learned about immune rejuvenation and its impact on conditions associated with chronic immune dysfunction. We know more than we ever have before about how to reduce chronic inflammation at its source through the support of selective immune cell autophagy/mitophagy and improved immune cell mitochondrial activity, followed by remodeling of the immune epigenome, and-ultimately-a reset of immune function.
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The Effects of Vegetarian and Vegan Diets on Gut Microbiota.
Tomova, A, Bukovsky, I, Rembert, E, Yonas, W, Alwarith, J, Barnard, ND, Kahleova, H
Frontiers in nutrition. 2019;6:47
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The difference in gut microbiota composition between individuals following vegan or vegetarian diets and those following omnivorous diets is well documented. A plant-based diet appears to be beneficial for human health by promoting the development of more diverse and stable microbial systems. This diversity appears to have an important association with BMI, obesity, and arterial compliance. This review highlights the effects of different diets, particularly plant-based diets, on the gut microbiota composition and production of microbial metabolites affecting the host health. The ratio between Bacteroidetes and Firmicutes is discussed and how different diets can change it. It explains how diet can affect the three main enterotypes: Prevotella, Bacteroides, and Ruminococcus. The food components proteins, carbohydrates, fats and polyphenols are discussed and how they influence gut microbiota. Up to date knowledge suggests that a plant-based diet may be an effective way to promote a diverse ecosystem of beneficial microbes that support overall health. However, due to the complexity and inter-individual differences, further research is required to fully characterize the interactions between diet, the microbiome, and health outcomes.
Abstract
The difference in gut microbiota composition between individuals following vegan or vegetarian diets and those following omnivorous diets is well documented. A plant-based diet appears to be beneficial for human health by promoting the development of more diverse and stable microbial systems. Additionally, vegans and vegetarians have significantly higher counts of certain Bacteroidetes-related operational taxonomic units compared to omnivores. Fibers (that is, non-digestible carbohydrates, found exclusively in plants) most consistently increase lactic acid bacteria, such as Ruminococcus, E. rectale, and Roseburia, and reduce Clostridium and Enterococcus species. Polyphenols, also abundant in plant foods, increase Bifidobacterium and Lactobacillus, which provide anti-pathogenic and anti-inflammatory effects and cardiovascular protection. High fiber intake also encourages the growth of species that ferment fiber into metabolites as short-chain fatty acids (SCFAs), including acetate, propionate, and butyrate. The positive health effects of SCFAs are myriad, including improved immunity against pathogens, blood-brain barrier integrity, provision of energy substrates, and regulation of critical functions of the intestine. In conclusion, the available literature suggests that a vegetarian/vegan diet is effective in promoting a diverse ecosystem of beneficial bacteria to support both human gut microbiome and overall health. This review will focus on effects of different diets and nutrient contents, particularly plant-based diets, on the gut microbiota composition and production of microbial metabolites affecting the host health.
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A Review of Dietary (Phyto)Nutrients for Glutathione Support.
Minich, DM, Brown, BI
Nutrients. 2019;11(9)
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Glutathione is made up of 3 amino acids (cysteine, glutamic acid and glycine) and plays important roles in the body, including oxidative stress reduction, supporting the immune system and contributing to detoxification processes. Evidence suggests that it is an important marker and target for treatment in many chronic, age-related diseases. This review article explores the evidence of nutritional strategies to improve glutathione status. The authors examine the evidence for supplementation of the precursors of glutathione as well as with various forms of supplemental glutathione itself, and the impacts on glutathione status and clinical impacts. Crucially, the review article provides information on dietary sources of precursors of glutathione and glutathione itself, which will provide Nutrition Practitioners with compelling information for use in clinic. Lean protein, brassica vegetables, polyphenol-rich fruits and vegetables, green tea, herbs and spices and omega-3 rich foods are all discussed in detail.
Abstract
Glutathione is a tripeptide that plays a pivotal role in critical physiological processes resulting in effects relevant to diverse disease pathophysiology such as maintenance of redox balance, reduction of oxidative stress, enhancement of metabolic detoxification, and regulation of immune system function. The diverse roles of glutathione in physiology are relevant to a considerable body of evidence suggesting that glutathione status may be an important biomarker and treatment target in various chronic, age-related diseases. Yet, proper personalized balance in the individual is key as well as a better understanding of antioxidants and redox balance. Optimizing glutathione levels has been proposed as a strategy for health promotion and disease prevention, although clear, causal relationships between glutathione status and disease risk or treatment remain to be clarified. Nonetheless, human clinical research suggests that nutritional interventions, including amino acids, vitamins, minerals, phytochemicals, and foods can have important effects on circulating glutathione which may translate to clinical benefit. Importantly, genetic variation is a modifier of glutathione status and influences response to nutritional factors that impact glutathione levels. This narrative review explores clinical evidence for nutritional strategies that could be used to improve glutathione status.
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Borrelia burgdorferi peptidoglycan is a persistent antigen in patients with Lyme arthritis.
Jutras, BL, Lochhead, RB, Kloos, ZA, Biboy, J, Strle, K, Booth, CJ, Govers, SK, Gray, J, Schumann, P, Vollmer, W, et al
Proceedings of the National Academy of Sciences of the United States of America. 2019;116(27):13498-13507
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Lyme disease is a varied, multisystem disorder caused by the spiral-shaped bacteria Borrelia burgdorferi (Bb). Advanced stages of the disease can present with oligoarthritis, most commonly involving the knee joints. Peptidoglycan (PG) is a compound that makes up the cell envelope of Bb and other bacteria. It acts as a microbe-associated molecular pattern, which can trigger the immune system and induces pro-inflammatory responses. This article summarises a series of cell, human, and animal studies supporting the theory that PG is a contributor to persistent Lyme’s arthritis (LA) far beyond the eradication of the pathogen. Significantly elevated inflammatory markers as well as antibodies to PG and Bb itself have been found in patients with LA before and after antibiotic therapy. The inflammatory response to Bb PG seems to be particularly high when compared to other bacteria. In summary, the authors suggest that PG accumulation in the joints and subsequent persistent inflammation contribute to LA and that targeting the specific inflammatory pathways involved may yield potential therapeutic interventions. This article could be of interest to those looking to understand more about the mechanisms and specific inflammatory responses involved in LA.
Abstract
Lyme disease is a multisystem disorder caused by the spirochete Borrelia burgdorferi A common late-stage complication of this disease is oligoarticular arthritis, often involving the knee. In ∼10% of cases, arthritis persists after appropriate antibiotic treatment, leading to a proliferative synovitis typical of chronic inflammatory arthritides. Here, we provide evidence that peptidoglycan (PG), a major component of the B. burgdorferi cell envelope, may contribute to the development and persistence of Lyme arthritis (LA). We show that B. burgdorferi has a chemically atypical PG (PGBb) that is not recycled during cell-wall turnover. Instead, this pathogen sheds PGBb fragments into its environment during growth. Patients with LA mount a specific immunoglobulin G response against PGBb, which is significantly higher in the synovial fluid than in the serum of the same patient. We also detect PGBb in 94% of synovial fluid samples (32 of 34) from patients with LA, many of whom had undergone oral and intravenous antibiotic treatment. These same synovial fluid samples contain proinflammatory cytokines, similar to those produced by human peripheral blood mononuclear cells stimulated with PGBb In addition, systemic administration of PGBb in BALB/c mice elicits acute arthritis. Altogether, our study identifies PGBb as a likely contributor to inflammatory responses in LA. Persistence of this antigen in the joint may contribute to synovitis after antibiotics eradicate the pathogen. Furthermore, our finding that B. burgdorferi sheds immunogenic PGBb fragments during growth suggests a potential role for PGBb in the immunopathogenesis of other Lyme disease manifestations.