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1.
Inflammatory Bowel Diseases and Food Additives: To Add Fuel on the Flames!
Marion-Letellier, R, Amamou, A, Savoye, G, Ghosh, S
Nutrients. 2019;11(5)
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Inflammatory Bowel Diseases (IBDs), such as Crohn’s disease (CD) and Ulcerative Colitis (UC) are becoming increasingly common. Diet is thought to play a role in the development of IBDs. The consumption of Ultra Processed Food (UPF) is increasing and has been associated with a higher risk of some chronic diseases. Food additives may be an aspect of UPF responsible for its harmful effects. This literature review examined the role of food additives in the development and severity of IBDs. The authors discuss how common food additives such as salt, emulsifiers, stabilisers, bulking agents, sweeteners, and food colouring may promote inflammation and disrupt gut bacteria. Metals and compounds found in food packaging such as aluminium and bisphenol A (BPA) may trigger intestinal permeability and increase inflammatory markers. Much of the evidence available is based on clinical trials on animals, whilst epidemiological studies on food additives and IBD risk are still limited. The authors concluded that the majority of food consumed by IBD patients should be home-cooked in order to reduce exposure to additives in the diet.
Abstract
Inflammatory bowel diseases (IBDs) develop in genetically predisposed individuals in response to environmental factors. IBDs are concomitant conditions of industrialized societies, and diet is a potential culprit. Consumption of ultra-processed food has increased over the last decade in industrialized countries, and epidemiological studies have found associations between ultra-processed food consumption and chronic diseases. Further studies are now required to identify the potential culprit in ultra-processed food, such as a poor nutritional composition or the presence of food additives. In our review, we will focus on food additives, i.e., substances from packaging in contact with food, and compounds formed during production, processing, and storage. A literature search using PubMed from inception to January 2019 was performed to identify relevant studies on diet and/or food additive and their role in IBDs. Manuscripts published in English from basic science, epidemiological studies, or clinical trials were selected and reviewed. We found numerous experimental studies highlighting the key role of food additives in IBD exacerbation but epidemiological studies on food additives on IBD risk are still limited. As diet is a modifiable environmental risk factor, this may offer a scientific rationale for providing dietary advice for IBD patients.
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Gut microbial metabolites in depression: understanding the biochemical mechanisms.
Caspani, G, Kennedy, S, Foster, JA, Swann, J
Microbial cell (Graz, Austria). 2019;6(10):454-481
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Major depressive disorder is a leading cause of disability and is linked to shortened life expectancy and suicide. Despite its prevalence, for near to a third of patients, long-term treatment options are ineffective. In addition to the primary presentation of persistent low mood, other emotional and physiological symptoms, researchers have also identified alterations in metabolism, hormones and the immune system. Furthermore, increasing evidence suggests that depression and depressive behaviour is also influenced by divergences in gut health and gut bacteria composition. With insights from animal and human research, this review highlights how the gut and gut bacteria-derived metabolites can directly or indirectly influence mood. Described are the pathways of how the gut and its microorganism communicate with the brain, the essential role the immune system has as part of the gut-brain communication, and the impact of low-grade, chronic inflammation on neurofunction. Comprehensive summaries are dedicated to how several metabolites or by-products from gut bacteria can influence the nervous system and gene expression in relation to depression. These include substances like neurotransmitters, short-chain fatty acids, tryptophan metabolites, lactate, bile acids, choline metabolites and folate. This article yields a detailed overview of how gut health and microbiota can influence neurofunction and mental health. The authors promote the idea of the gut as a suitable target for the management of depressive disorders, whilst also eluding to the current limitations and need for further research.
Abstract
Gastrointestinal and central function are intrinsically connected by the gut microbiota, an ecosystem that has co-evolved with the host to expand its biotransformational capabilities and interact with host physiological processes by means of its metabolic products. Abnormalities in this microbiota-gut-brain axis have emerged as a key component in the pathophysiology of depression, leading to more research attempting to understand the neuroactive potential of the products of gut microbial metabolism. This review explores the potential for the gut microbiota to contribute to depression and focuses on the role that microbially-derived molecules - neurotransmitters, short-chain fatty acids, indoles, bile acids, choline metabolites, lactate and vitamins - play in the context of emotional behavior. The future of gut-brain axis research lies is moving away from association, towards the mechanisms underlying the relationship between the gut bacteria and depressive behavior. We propose that direct and indirect mechanisms exist through which gut microbial metabolites affect depressive behavior: these include (i) direct stimulation of central receptors, (ii) peripheral stimulation of neural, endocrine, and immune mediators, and (iii) epigenetic regulation of histone acetylation and DNA methylation. Elucidating these mechanisms is essential to expand our understanding of the etiology of depression, and to develop new strategies to harness the beneficial psychotropic effects of these molecules. Overall, the review highlights the potential for dietary interventions to represent such novel therapeutic strategies for major depressive disorder.
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Tryptophan Metabolism in Inflammaging: From Biomarker to Therapeutic Target.
Sorgdrager, FJH, Naudé, PJW, Kema, IP, Nollen, EA, Deyn, PP
Frontiers in immunology. 2019;10:2565
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Inflammation is a normal physiological process activated by the immune system in response to injury or infection. As we age, the immune system changes and the balance between pro- and anti-inflammatory agents can shift. This causes a chronic inflammatory state referred to as inflammaging. The rate of inflammaging is strongly associated with age-related disability, disease and mortality. The way in which the essential amino acid tryptophan (Trp) is broken down affects inflammation. If it is converted to kynurenine (Kyn) and its metabolites, inflammation is modulated. Studies have shown that the Kyn/Trp ratio, measured in blood, is strongly associated with ageing in humans. It could therefore be a useful marker to predict the onset of age-related diseases. This review discusses the metabolism of Trp and the links to inflammation. The authors hypothesize how intervening in these pathways could impact health- and lifespan. Future studies are needed to confirm the value of Trp metabolism as a biomarker for (un)healthy ageing and as drug target for inflammaging-related disease.
Abstract
Inflammation aims to restore tissue homeostasis after injury or infection. Age-related decline of tissue homeostasis causes a physiological low-grade chronic inflammatory phenotype known as inflammaging that is involved in many age-related diseases. Activation of tryptophan (Trp) metabolism along the kynurenine (Kyn) pathway prevents hyperinflammation and induces long-term immune tolerance. Systemic Trp and Kyn levels change upon aging and in age-related diseases. Moreover, modulation of Trp metabolism can either aggravate or prevent inflammaging-related diseases. In this review, we discuss how age-related Kyn/Trp activation is necessary to control inflammaging and alters the functioning of other metabolic faiths of Trp including Kyn metabolites, microbiota-derived indoles and nicotinamide adenine dinucleotide (NAD+). We explore the potential of the Kyn/Trp ratio as a biomarker of inflammaging and discuss how intervening in Trp metabolism might extend health- and lifespan.
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The skin microbiome in psoriatic disease: A systematic review and critical appraisal.
Yerushalmi, M, Elalouf, O, Anderson, M, Chandran, V
Journal of translational autoimmunity. 2019;2:100009
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Psoriasis is a common inflammatory skin disease that results in patches of dry, scaly skin that can be itchy or sore. Psoriatic arthritis is an inflammatory arthritis that affects up to 30% of psoriasis patients. The role of skin bacteria (the skin microbiome) is not well understood. This systematic review summarised the literature on the microbiome in psoriatic disease. The researchers looked at nine studies: seven on psoriasis only, and two studies comparing the microbiome characteristics between psoriasis and psoriatic arthritis. Compared to healthy controls, the skin of psoriasis patients demonstrated a decreased species diversity, higher relative abundances of Firmicutes, and lower relative abundances of Actinobacteria. Less conclusive were genus-level results, which demonstrated trends towards increased Streptococcus, Staphylococcus, and Corynebacterium, and decreased Propionibacterium in the skin of psoriasis patients versus healthy controls. However, the studies’ designs and methodologies varied, and therefore the researchers concluded that further research into the role of the skin microbiome in psoriatic disease is needed.
Abstract
BACKGROUND Psoriasis affects 1-3% of the Canadian population. Psoriatic arthritis (PsA), the most common comorbidity of psoriasis, affects up to 30% of psoriasis patients. The skin microbiome is hypothesized to play a role in the pathogenesis of psoriatic disease (PsD-psoriasis and PsA). OBJECTIVE To summarize the current state of literature on the skin microbiome in PsD. METHODS A systematic review was performed using searches in Ovid, Medline, Embase, Medline Epub Ahead of Print and In-Process & Other Non-Indexed Citations, and Cochrane Central Register of Controlled Trials (CENTRAL). Search was limited to humans and English language, with no limits for date or publication type. RESULTS Of 4,032 citations identified, 9 studies met inclusion criteria (7 on psoriasis only and 2 studies compared the microbiome characteristics between psoriasis and PsA). Compared to healthy controls, lesions demonstrated a decreased alpha diversity, higher relative abundances of Firmicutes, and lower relative abundances of Actinobacteria. Less conclusive were genus-level results, which nonetheless demonstrated trends towards increased Streptococcus, Staphylococcus, and Corynebacterium and decreased Propionibacterium in lesions vs. control. LIMITATIONS Study designs were heterogeneous, including sampling technique and exclusion criteria. CONCLUSIONS Phyla- and selected genus-level characteristic of the psoriatic microbiome are presented; further research is warranted.
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Fermented Foods: Definitions and Characteristics, Impact on the Gut Microbiota and Effects on Gastrointestinal Health and Disease.
Dimidi, E, Cox, SR, Rossi, M, Whelan, K
Nutrients. 2019;11(8)
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Fermented foods have grown in popularity due to their proposed health benefits but there is limited clinical evidence for the effectiveness of most fermented foods in gastrointestinal health. This review paper looks at non-dairy fermented foods which have been studied in at least one RCT: kefir, sauerkraut, natto, and sourdough bread. The health benefits are attributed to the high ratio of probiotic microorganisms, metabolites, or ability to convert compounds into active metabolites, as well as prebiotics and vitamins contained in these foods. Kimchi has the greatest evidence from epidemiological and case control studies investigating risk of gastric cancers. Different food composition of kimchi is shown to both increase and decrease risks, whilst it had no impact on H. pylori levels. There were no studies on kefir in functional bowel disorders however, it was shown to help lactose malabsorption and reduce H. pylori levels. A small RCT on Sauerkraut showed it reduced IBS severity in patients and increased in vitro activity of key liver and kidney detoxifying enzymes. There are small pockets of data that show that tempeh may influence gut microbiota in humans, and that natto may increase bifidobacterial and short-chain fatty acids in healthy volunteers. There are numerous limited cohort studies on miso and cancer risk but no studies on gastrointestinal conditions. Finally, sourdough was shown to reduce FODMAPS and be better tolerated in IBS patients, reducing bloating, nausea and discomfort. Overall, all the studies provide insufficient evidence on fermented foods and gastrointestinal health.
Abstract
Fermented foods are defined as foods or beverages produced through controlled microbial growth, and the conversion of food components through enzymatic action. In recent years, fermented foods have undergone a surge in popularity, mainly due to their proposed health benefits. The aim of this review is to define and characterise common fermented foods (kefir, kombucha, sauerkraut, tempeh, natto, miso, kimchi, sourdough bread), their mechanisms of action (including impact on the microbiota), and the evidence for effects on gastrointestinal health and disease in humans. Putative mechanisms for the impact of fermented foods on health include the potential probiotic effect of their constituent microorganisms, the fermentation-derived production of bioactive peptides, biogenic amines, and conversion of phenolic compounds to biologically active compounds, as well as the reduction of anti-nutrients. Fermented foods that have been tested in at least one randomised controlled trial (RCT) for their gastrointestinal effects were kefir, sauerkraut, natto, and sourdough bread. Despite extensive in vitro studies, there are no RCTs investigating the impact of kombucha, miso, kimchi or tempeh in gastrointestinal health. The most widely investigated fermented food is kefir, with evidence from at least one RCT suggesting beneficial effects in both lactose malabsorption and Helicobacter pylori eradication. In summary, there is very limited clinical evidence for the effectiveness of most fermented foods in gastrointestinal health and disease. Given the convincing in vitro findings, clinical high-quality trials investigating the health benefits of fermented foods are warranted.
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Salmonella Infection in Chronic Inflammation and Gastrointestinal Cancer.
Zha, L, Garrett, S, Sun, J
Diseases (Basel, Switzerland). 2019;7(1)
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Salmonella is a group of bacteria that is normally associated with food poisoning. In 2% to 5% of people with Salmonella food poisoning, the bacteria remain in the body, leading to long-term infection, which has been linked to various health problems. This literature review looked at the link between Salmonella infection and the development of diseases such as inflammatory bowel disease (IBD), gall bladder cancer and colon cancer. The authors describe how long-term Salmonella infection plays a role in several biological processes, such as stem cell maintenance, host cell transformation, and gut dysbiosis. Leaky gut, dysbiosis and inflammation are induced by the bacteria and contribute to the development of cancer. The authors conclude that more studies are needed to further understand the relationship between Salmonella infections and the risk of colon cancer.
Abstract
Salmonella not only causes acute infections, but can also cause patients to become chronic "asymptomatic" carriers. Salmonella has been verified as a pathogenic factor that contributes to chronic inflammation and carcinogenesis. This review summarizes the acute and chronic Salmonella infection and describes the current research progress of Salmonella infection contributing to inflammatory bowel disease and cancer. Furthermore, this review explores the underlying biological mechanism of the host signaling pathways manipulated by Salmonella effector molecules. Using experimental animal models, researchers have shown that Salmonella infection is related to host biological processes, such as host cell transformation, stem cell maintenance, and changes of the gut microbiota (dysbiosis). Finally, this review discusses the current challenges and future directions in studying Salmonella infection and its association with human diseases.
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Vitamin D Supplementation in Central Nervous System Demyelinating Disease-Enough Is Enough.
Häusler, D, Weber, MS
International journal of molecular sciences. 2019;20(1)
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Vitamin D is associated with a reduced risk and severity of multiple sclerosis (MS). However, whether supplementing vitamin D level alters disease severity, is a matter of ongoing debate. This review looks at both clinical and pre-clinical evidence for supplementing vitamin D in people with MS. In vitro experiments show that vitamin D and its metabolites can alter function of various immune cells, mostly via interaction with vitamin D receptors (VDR). Results from human clinical trials, however, are mixed. Preclinical evidence suggests that high dose vitamin D supplementation, when leading to hypercalcaemia, a potentially serious side effect of excessive vitamin D intake, may worsen MS. The authors also review research which suggests mechanisms by which sun exposure can improve MS symptoms independent of vitamin D production. The authors conclude that moderate sun exposure, combined with adequate dietary intake of vitamin D, and in conjunction with a regular assessment of vitamin D serum levels (to avoid hypercalcaemia), might be the best strategy for patients with MS.
Abstract
The exact cause of multiple sclerosis (MS) remains elusive. Various factors, however, have been identified that increase an individual's risk of developing this central nervous system (CNS) demyelinating disease and are associated with an acceleration in disease severity. Besides genetic determinants, environmental factors are now established that influence MS, which is of enormous interest, as some of these contributing factors are relatively easy to change. In this regard, a low vitamin D status is associated with an elevated relapse frequency and worsened disease course in patients with MS. The most important question, however, is whether this association is causal or related. That supplementing vitamin D in MS is of direct therapeutic benefit, is still a matter of debate. In this manuscript, we first review the potentially immune modulating mechanisms of vitamin D, followed by a summary of current and ongoing clinical trials intended to assess whether vitamin D supplementation positively influences the outcome of MS. Furthermore, we provide emerging evidence that excessive vitamin D treatment via the T cell-stimulating effect of secondary hypercalcemia, could have negative effects in CNS demyelinating disease. This jointly merges into the balancing concept of a therapeutic window of vitamin D in MS.
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Role of Probiotics in Non-alcoholic Fatty Liver Disease: Does Gut Microbiota Matter?
Xie, C, Halegoua-DeMarzio, D
Nutrients. 2019;11(11)
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Non-alcoholic fatty liver disease (NAFLD) is characterised by an excessive accumulation of fat in the liver tissue, without excessive alcohol consumption, and appears to be related to metabolic syndrome. It is thought to have a prevalence of 25% globally and there are no pharmacological treatments available. This review discusses the connection between the gut microbiota (GM) and NAFLD. Various mechanisms by which the GM may be involved in the development of NAFLD are discussed. As probiotics and prebiotics can normalise GM and reverse dysbiosis their use may benefit patients with NAFLD. This has been confirmed in animal models. The authors review 26 randomised controlled trials (RCTs) of probiotics and/or prebiotics in the treatment of NAFLD which evaluate biochemical markers, as well as five meta-analyses, and found that overall there is strong evidence that probiotics and/or prebiotics can lower ALT and AST (markers of NAFLD), although results for other biochemical markers were mixed. They also reviewed RCTs assessing NAFLD by imaging and histological means, and again found benefits from probiotic and/or prebiotic supplementation.
Abstract
Non-alcoholic fatty liver disease (NAFLD) is the hepatic consequence of metabolic syndrome, which often also includes obesity, diabetes, and dyslipidemia. The connection between gut microbiota (GM) and NAFLD has attracted significant attention in recent years. Data has shown that GM affects hepatic lipid metabolism and influences the balance between pro/anti-inflammatory effectors in the liver. Although studies reveal the association between GM dysbiosis and NAFLD, decoding the mechanisms of gut dysbiosis resulting in NAFLD remains challenging. The potential pathophysiology that links GM dysbiosis to NAFLD can be summarized as: (1) disrupting the balance between energy harvest and expenditure, (2) promoting hepatic inflammation (impairing intestinal integrity, facilitating endotoxemia, and initiating inflammatory cascades with cytokines releasing), and (3) altered biochemistry metabolism and GM-related metabolites (i.e., bile acid, short-chain fatty acids, aromatic amino acid derivatives, branched-chain amino acids, choline, ethanol). Due to the hypothesis that probiotics/synbiotics could normalize GM and reverse dysbiosis, there have been efforts to investigate the therapeutic effect of probiotics/synbiotics in patients with NAFLD. Recent randomized clinical trials suggest that probiotics/synbiotics could improve transaminases, hepatic steatosis, and reduce hepatic inflammation. Despite these promising results, future studies are necessary to understand the full role GM plays in NAFLD development and progression. Additionally, further data is needed to unravel probiotics/synbiotics efficacy, safety, and sustainability as a novel pharmacologic approaches to NAFLD.
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Beta Glucan: Supplement or Drug? From Laboratory to Clinical Trials.
Vetvicka, V, Vannucci, L, Sima, P, Richter, J
Molecules (Basel, Switzerland). 2019;24(7)
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Beta glucans, β-1,3-glucans (glucans) are chains of sugars (polysaccharides) naturally occurring in the cell walls of plants such as cereals, bacteria and fungi. They are gaining attention not only as an important food supplement but also as an immunostimulant and potential drug. It has been known since prehistoric times that mushrooms have medicinal properties. Glucans effect various branches of the immune system and there are numerous animal and human studies showing remarkable activity against a wide variety of tumours. This paper represents an up-to-date review of glucans and their role in various immune reactions and the treatment of cancer. It also cites studies showing their potential use for wound healing and skin health, chronic respiratory problems in children, alleviation of allergic problems and reducing cholesterol levels. Additional lesser-known effects of glucan include improvements in colitis, obesity, or Lyme disease The authors conclude that glucans are an important immunomodulator. They believe that glucans will soon move from food supplement to widely accepted drug.
Abstract
Glucans are part of a group of biologically active natural molecules and are steadily gaining strong attention not only as an important food supplement, but also as an immunostimulant and potential drug. This paper represents an up-to-date review of glucans (β-1,3-glucans) and their role in various immune reactions and the treatment of cancer. With more than 80 clinical trials evaluating their biological effects, the question is not if glucans will move from food supplement to widely accepted drug, but how soon.
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Medical and Dietary Uses of N-Acetylcysteine.
Šalamon, Š, Kramar, B, Marolt, TP, Poljšak, B, Milisav, I
Antioxidants (Basel, Switzerland). 2019;8(5)
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N-Acetylcysteine (NAC) is an antioxidant naturally found in plants of the Allium species such as onions. As well as having antioxidant and anti-inflammatory properties, it is also needed to make glutathione which is an important antioxidant in cells. NAC has been used as a drug since the 1960s and is a popular dietary supplement. NAC is considered safe but the results of clinical trials are controversial or incomplete. This aim of this review is to provide a balanced view of further uses of NAC as a dietary supplement. It discusses the antioxidant properties in relation to conditions such as heart disease, diabetes and ageing; its medical uses, in the complementary treatment of cancer, as a sports supplement and as an anti-aging supplement. More information is needed on NAC and further clinical trials looking at its use in neurodegenerative diseases, addiction, and mental health disorders are underway. This may be relevant to the supplement users and may also help people suffering from chronic degenerative conditions.
Abstract
N-acetylcysteine (NAC), a plant antioxidant naturally found in onion, is a precursor to glutathione. It has been used as a drug since the 1960s and is listed on the World Health Organization (WHO) Model List of Essential Medicines as an antidote in poisonings. There are numerous other uses or proposed uses in medicine that are still in preclinical and clinical investigations. NAC is also used in food supplements and cosmetics. Despite its abundant use, there are projections that the NAC global market will grow in the next five years; therefore, the purpose of this work is to provide a balanced view of further uses of NAC as a dietary supplement. Although NAC is considered a safe substance, the results among clinical trials are sometimes controversial or incomplete, like for many other antioxidants. More clinical trials are underway that will improve our understanding of NAC applicability.