Fermented foods, microbiota, and mental health: ancient practice meets nutritional psychiatry

The purposeful application of fermentation in food and beverage preparation, as a means to provide palatability, nutritional value, preservative, and medicinal properties, is an ancient practice. Fermented foods and beverages continue to make a significant contribution to the overall patterns of traditional dietary practices. As our knowledge of the human microbiome increases, including its connection to mental health (for example, anxiety and depression), it is becoming increasingly clear that there are untold connections between our resident microbes and many aspects of physiology. Of relevance to this research are new findings concerning the ways in which fermentation alters dietary items pre-consumption, and in turn, the ways in which fermentation-enriched chemicals (for example, lactoferrin, bioactive peptides) and newly formed phytochemicals (for example, unique flavonoids) may act upon our own intestinal microbiota profile. Here, we argue that the consumption of fermented foods may be particularly relevant to the emerging research linking traditional dietary practices and positive mental health. The extent to which traditional dietary items may mitigate inflammation and oxidative stress may be controlled, at least to some degree, by microbiota. It is our contention that properly controlled fermentation may often amplify the specific nutrient and phytochemical content of foods, the ultimate value of which may associated with mental health; furthermore, we also argue that the microbes (for example, Lactobacillus and Bifidobacteria species) associated with fermented foods may also influence brain health via direct and indirect pathways

Intestinal microbiota, probiotics and mental health: from Metchnikoff to modern advances: Part II – contemporary contextual research

In recent years there has been a renewed interest concerning the ways in which the gastrointestinal tract – its functional integrity and microbial residents – might influence human mood (e.g. depression) and behavioral disorders. Once a hotbed of scientific interest in the early 20th century, this area lay dormant for decades, in part due to its association with the controversial term ‘autointoxication’. Here we review contemporary findings related to intestinal permeability, small intestinal bacterial overgrowth, lipopolysaccharide endotoxin (LPS) exposure, D-lactic acid, propionic acid, and discuss their relevance to microbiota and mental health. In addition, we include the context of modern dietary habits as they relate to depression, anxiety and their potential interaction with intestinal microbiota

Intestinal Microbiota, Probiotics and Mental Health: From Metchnikoff to Modern Advances: Part III – Convergence toward Clinical Trials

Rapid scientific and technological advances have allowed for a more detailed understanding of the relevance of intestinal microbiota, and the entire body-wide microbiome, to human health and well-being. Rodent studies have provided suggestive evidence that probiotics (e.g. lactobacillus and bifidobacteria) can influence behavior. More importantly, emerging clinical studies indicate that the administration of beneficial microbes, via supplementation and/or fecal microbial transplant (FMT), can influence end-points related to mood state (glycemic control, oxidative status, uremic toxins), brain function (functional magnetic resonance imaging fMRI), and mental outlook (depression, anxiety). However, despite the advances in the area of gastro-biological psychiatry, it becomes clear that there remains an urgent need to explore the value of beneficial microbes in controlled clinical investigations. With the history explored in this series, it is fair to ask if we are now on the cusp of major clinical breakthroughs, or are we merely in the quicksand of Autointoxication II

Intestinal Microbiota, Probiotics and Mental Health: From Metchnikoff to Modern Advances: Part I – Autointoxication Revisited

Mental health disorders, depression in particular, have been described as a global epidemic. Research suggests that a variety of lifestyle and environmental changes may be driving at least some portion of the increased prevalence. One area of flourishing research involves the relationship between the intestinal microbiota (as well as the related functional integrity of the gastrointestinal tract) and mental health. In order to appreciate the recent scientific gains in this area, and its potential future directions, it is critical to review the history of the topic. Probiotic administration (e.g. Lactobacillus) and fecal microbiota transfer for conditions associated with depression and anxiety is not a new concept. Here, in the first of a 3-part series, we begin by reviewing the origins of the contemporary research, providing a critical appraisal of what has become a revisionist history of the controversial term ‘autointoxication’. We argue that legitimate interests in the gut-brain-microbiota connection were obscured for decades by its association with a narrow historical legacy. Historical perspectives provide a very meaningful context to the current state of the contemporary research as outlined in parts II and III

Inflammation causes tissue-specific depletion of vitamin B(6)

Previously we observed strong and consistent associations between vitamin B(6 )status and several indicators of inflammation in patients with rheumatoid arthritis. Clinical indicators, including the disability score, the length of morning stiffness, and the degree of pain, and biochemical markers, including the erythrocyte sedimentation rate and C-reactive protein levels, were found to be inversely correlated with circulating vitamin B(6 )levels. Such strong associations imply that impaired vitamin B(6 )status in these patients results from inflammation. In the present study we examined whether inflammation directly alters vitamin B(6 )tissue contents and its excretion in vivo. A cross-sectional case-controlled human clinical trial was performed in parallel with experiments in an animal model of inflammation. Plasma and erythrocyte and pyridoxal 5'-phosphate concentrations, urinary 4-pyridoxic acid excretion, and the activity coefficient of erythrocyte aspartate aminotransferase were compared between patients and healthy subjects. Adjuvant arthritis was induced in rats for investigating hepatic and muscle contents as well as the urinary excretion of vitamin B(6 )during acute and chronic inflammation. Patients with rheumatoid arthritis had low plasma pyridoxal 5'-phosphate compared with healthy control subjects, but normal erythrocyte pyridoxal 5'-phosphate and urinary 4-pyridoxic acid excretion. Adjuvant arthritis in rats did not affect 4-pyridoxic acid excretion or muscle storage of pyridoxal 5'-phosphate, but it resulted in significantly lower pyridoxal 5'-phosphate levels in circulation and in liver during inflammation. Inflammation induced a tissue-specific depletion of vitamin B(6). The low plasma pyridoxal 5'-phosphate levels seen in inflammation are unlikely to be due to insufficient intake or excessive vitamin B(6 )excretion. Possible causes of decreased levels of vitamin B(6 )are discussed

Plasma total homocysteine and macrovascular complications are associated with food and nutrient intake in patients with Type II diabetes mellitus

The present study was conducted to document the association between plasma homocysteine levels and the presence of macrovascular angiopathy with food and nutrient intake patterns among patients with Type II diabetes mellitus in Korea. Plasma total homocysteine concentration was analyzed by HPLC-fluorescence detector method in 127 patients with non-insulin dependent diabetes mellitus. Logistic regression analyses were performed respectively to study the association of plasma homocysteine levels with clinical and dietary characteristics and macroangiopathy (MA). The average plasma homocysteine level of patients with MA was 14.2 µmol/l, which was significantly higher than that of patients without MA (11.4 µmol/l). The proportions of patients with MA showed a significant difference, being 32.3% in hyperhomocysteinemic (>14.0 µmol/l) patients and 13.5% in others with homocysteine levels lower than 14.0 µmol/l. Odds ratios for macroangiopathy by tertile increase of plasma homocysteine concentration were 1.633 (Q2) and 4.831 (Q3), when adjusted for age, sex, and cigarette smoking. Patients with MA consumed reduced amounts of vitamin B1, B2, and folate. The results indicate that the plasma homocysteine levels are significantly increased in NIDDM patients who have macroangiopathy. Dietary management such as increased fruits and vegetables and decreased potatoes and starches might be beneficial for the prevention of macroangiopathy in diabetic patients

Distribution of plasma folate forms in hemodialysis patients receiving high daily doses of l-folinic or folic acid

Distribution of plasma folate forms in hemodialysis patients receiving high daily doses of l-folinic or folic acid.BackgroundWe have previously reported that a daily oral high dose of l-folinic acid for the treatment of hyperhomocysteinemia in hemodialysis patients does not provide significantly greater reduction in fasting total homocysteine (tHcy) levels than an equimolar dose of folic acid. The present study uses the affinity/HPLC method to analyze the distribution of plasma folate forms in patients who received l-folinic acid versus those who received folic acid. This was done to investigate claims that renal insufficiency is associated with impaired folate interconversion, a stance that is supportive of the premise that tHcy lowering in these patients is more efficacious with folinic acid and other reduced folates, than folic acid.MethodsForty-eight chronic and stable hemodialysis patients were block-randomized, based on their screening predialysis tHcy levels, sex, and dialysis center, into two groups treated for 12 weeks with oral folic acid at 15 mg/day or an equimolar amount (20 mg/day) of oral l-folinic acid. All 48 subjects also received 50 mg/day of oral vitamin B6 and 1 mg/day of oral vitamin B12. Folate distribution was determined in plasma of 46 participants (Folinic acid group, N = 22; Folic acid group, N = 24) by using the affinity/HPLC method, with electrochemical (coulometric) detection.ResultsBoth groups had similar baseline geometric means of plasma total folate and similar folate forms distribution. Following treatment, both groups demonstrated similar marked elevation in plasma total folate (geometric mean of the increase: Folinic acid group, +337 ng/mL; Folic acid group, +312 ng/mL; P = 0.796). In the folinic acid-treated group, practically all of the increase in total folate was due to 5-methyltetrahydrofolate. In the folic acid-treated group 5-methyltetrahydrofolate accounted for 35% of the increase in total folate and the remainder was unmethylated folic acid.ConclusionsData from the present findings suggest that defects in folate absorption or impairment in folate interconversion are not the cause of the persistent hyperhomocysteinemia in hemodialysis patients

Significantly elevated levels of plasma nicotinamide, pyridoxal, and pyridoxamine phosphate levels in obese Emirati population : a cross-sectional study

Water-soluble vitamins like B3 (nicotinamide), B6 (pyridoxine), and B9 (folic acid) are of utmost importance in human health and disease, as they are involved in numerous critical metabolic reactions. Not surprisingly, deficiencies of these vitamins have been linked to various disease states. Unfortunately, not much is known about the physiological levels of B6 vitamers and vitamin B3 in an ethnically isolated group (such as an Emirati population), as well as their relationship with obesity. The aim of the present study was to quantify various B6 vitamers, as well as B3, in the plasma of obese and healthy Emirati populations and to examine their correlation with obesity. A sensitive and robust HPLC-MS/MS-based method was developed for the simultaneous quantitation of five physiologically relevant forms of vitamin B6, namely pyridoxal, pyridoxine, pyridoxamine, pyridoxamine phosphate, and pyridoxal phosphate, as well as nicotinamide, in human plasma. This method was used to quantify the concentrations of these vitamers in the plasma of 57 healthy and 57 obese Emirati volunteers. Our analysis showed that the plasma concentrations of nicotinamide, pyridoxal, and pyridoxamine phosphate in the obese Emirati population were significantly higher than those in healthy volunteers (p < 0.0001, p = 0.0006, and p = 0.002, respectively). No significant differences were observed for the plasma concentrations of pyridoxine and pyridoxal phosphate. Furthermore, the concentrations of some of these vitamers in healthy Emirati volunteers were significantly different than those published in the literature for Western populations, such as American and European volunteers. This initial study underscores the need to quantify micronutrients in distinct ethnic groups, as well as people suffering from chronic metabolic disorders

Pre-Diagnostic Leukocyte Genomic DNA Methylation and the Risk of Colorectal Cancer in Women

Background: Abnormal one-carbon metabolism may lead to general genomic (global) hypomethylation, which may predispose an individual to the development of colorectal neoplasia. Methods: We evaluated the association between pre-diagnostic leukocyte genomic DNA methylation level and the risk of colorectal cancer in a nested case-control study of 358 colorectal cancer cases and 661 matched controls within the all-female cohort of the Nurses’ Health Study (NHS). Among control subjects, we further examined major plasma components in the one-carbon metabolism pathway in relation to genomic DNA methylation level. Liquid chromatography/tandem mass spectrometry was used to examine leukocyte genomic DNA methylation level. We calculated odds ratios (ORs) and 95% confidence intervals (95% CIs) using logistic regression. Results: Overall genomic DNA methylation level was not associated with the risk of colorectal cancer (p for trend, 0.45). Compared with women in the lowest quintile of methylation, the multivariate OR of colorectal cancer risk was 1.32 (95% CI, 0.82–2.13) for those in the highest quintile. We did not find significant associations between major plasma components of one-carbon metabolism or risk factors for colorectal cancer and genomic DNA methylation level (all p for trend >0.05). Also, neither one-carbon metabolism-related plasma components nor well-known risk factors for colorectal cancer modified the association between genomic DNA methylation level and the risk of colorectal cancer (all p for interaction >0.05). Conclusions: We found no evidence that hypomethylation of leukocyte genomic DNA increases risk of colorectal cancer among women. Additional studies are needed to investigate the association between pre-diagnostic genomic DNA methylation level and colorectal cancer risk among diverse populations