ABSTRACT. W e studied properties of saliva and of dental plaque which affect the caries process in an effort to understand the low prevalence of caries in patients with chronic renal failure. Plaque pH, before and following carbohydrate exposure, saliva pEI, and saliva composition were evaluated in children and adolescents with chronic renal failure (n = 10) and successful renal transplantation (n = 1 I), and in two comparison groups of healthy children with few caries (n = 15) and numerous caries (n = 15).Salivary urea nitrogen concentration was elevated in all subjects with elevated serum urea nitrogen concentration. Chronic renal failure subjects had significantly higher salivary urea nitrogen concentration than transplanted subjects. Plaque p H correlated directly with salivary urea nitrogen concentration and was significantly more alkaline in chronic renal failure than transplant or comparison groups. Salivary urea nitrogen concentration accounted for the majority of variability in plaque pH, salivary p H and salivary phosphorous contributed negligibly. Absolute p H drop following carbohydrate exposure did not differ among groups, but because baseline plaque p H was elevated for chronic renal failure subjects, minimum p H did not attain Received February 5, 1985; accepted March 13,1985. cariogenic levels. Our data support the hypothesis that the relative paucity of caries in patients with chronic renal failure results from alteration of plaque by metabolic end products of urea metabolism. Our data further suggest that transplanted patients whose renal function is normal may be a t increased risk of caries, especially if enamel hypoplasia is present and oral hygiene is poor. (Pediatr Res 19: 796-799,1985)Abbreviations CRF, chronic renal failure SalUN, salivary urea nitrogen concentration Children with CRF have relatively few dental caries (1, 2) despite common occurrence of conditions which should increase risk of caries. Poor oral hygiene (3,4) and enamel hypoplasia (1, 2) are prevalent in CRF, and dietary supplementation of calories (5) results in cariogenic diets for many CRF patients. In an effort to explain low caries prevalence we designed a study to evaluate properties of plaque and saliva which might affect the caries process.Demineralination and erosion of enamel by organic acid are major factors in caries development (6). Plaque bacteria produce organic acid as a product of carbohydrate metabolism (7). In

The gut microbiota is a potential environmental factor that influences the development of multiple sclerosis (MS). We and others have demonstrated that patients with MS and healthy individuals have distinct gut microbiomes. However, the pathogenic relevance of these differences remains unclear. Previously, we showed that bacteria that metabolize isoflavones are less abundant in patients with MS, suggesting that isoflavone-metabolizing bacteria might provide protection against MS. Here, using a mouse model of MS, we report that an isoflavone diet provides protection against disease, which is dependent on the presence of isoflavone-metabolizing bacteria and their metabolite equol. Notably, the composition of the gut microbiome in mice fed an isoflavone diet exhibited parallels to healthy human donors, whereas the composition in those fed an isoflavone-free diet exhibited parallels to patients with MS. Collectively, our study provides evidence that dietary-induced gut microbial changes alleviate disease severity and may contribute to MS pathogenesis.

No abstract

No abstract

Multiple sclerosis (MS) is an autoimmune demyelinating disease of the CNS that is linked with both genetic and environmental factors. A Western-style diet rich in fat and simple sugars is hypothesized as a potential factor contributing to the increased incidence of inflammatory autoimmune diseases, such as MS, in developed countries. Although the adverse effects of a high-fat diet in MS have been studied extensively, the effect of a fructose-rich diet (FRD) on MS etiology is unknown. We hypothesized that an FRD will alter the gut microbiome, influence immune populations, and negatively impact disease in experimental autoimmune encephalomyelitis (EAE), an animal model of MS. To test this, we fed C57BL/6 mice either an FRD or normal feed for 4 or 12 wk and analyzed the effect of an FRD on gut microbiota, immune populations, and EAE. An FRD significantly influenced the gut microbiota, with reduced abundance of beneficial bacteria and enrichment of potentially proinflammatory bacteria. We also observed immune modulation in the gut and periphery. Of particular interest was a population of Helios−RORγt+Foxp3+CD4+ T cells that was enriched in the small intestine lamina propria of FRD-fed mice. However, despite gut microbiota and immune modulations, we observed only a subtle effect of an FRD on EAE severity. Overall, our data suggest that in C57Bl6/J mice, an FRD modulates the gut microbiota and immune system without significantly impacting myelin oligodendrocyte glycoprotein 35–55/CFA-induced EAE.

Multiple sclerosis (MS) is an autoimmune demyelinating disease of the central nervous system which may be influenced by gut bacteria-produced metabolites. We have shown that isoflavone-metabolizing bacteria are less abundant in MS patients as compared to healthy individuals and loss of these bacteria leads to increased disease severity in experimental autoimmune encephalomyelitis (EAE), a mouse model of MS. Isoflavone metabolites can modulate the immune response through binding to estrogen receptors α and β (ERα and ERβ). Thus, we aim to investigate the role of ERα and ERβ in isoflavone-mediated disease protection in EAE by determining ER expression on immune and intestinal epithelial cells as well as receptor specificity for isoflavone-mediated protection in EAE. We hypothesize that isoflavone metabolites induce an anti-inflammatory state via engagement of ERs and that reduction/absence of these molecules may predispose patients to MS development and/or severity. To test this, we administered an isoflavone-containing diet to mice and induced EAE. Mice fed an isoflavone-containing diet developed milder disease than mice fed an isoflavone-free diet while also exhibiting higher expression of ERα, but not ERβ, in the gut. Surprisingly, there was no change in ERβ expression in splenic CD4+ or CD8+ T-cells of mice fed an isoflavone-free versus an isoflavone-containing diet. Mice administered equol also exhibited milder disease than controls. Ongoing experiments using chemical or genetic inhibition of ERα and ERβ signaling will determine the role of these receptors in EAE disease amelioration. Our results suggest that bacterial metabolism of isoflavones leads to EAE disease suppression through utilization of estrogen receptors. Supported by grants from NIH (T32AI007485, 1R01AI137075-01) and a generous gift from Margaret Heppelmann and Michael Wacek.

The gut-brain axis may contribute to the pathophysiology of neurodevelopmental disorders, yet it is often unclear how risk genes associated with these disorders affect gut physiology in a manner that could impact microbial colonization. We addressed this question using Drosophila melanogaster with a null mutation in kismet, the ortholog of chromodomain helicase DNA-binding protein (CHD) family members CHD7 and CHD8. In humans, CHD7 and CHD8 are risk genes for neurodevelopmental disorders with co-occurring gastrointestinal symptoms. We found kismet mutant flies have a significant increase in gastrointestinal transit time, indicating functional homology of kismet with CHD7/CHD8 in vertebrates. To measure gut tissue mechanics, we used a high-precision force transducer and length controller, capable of measuring forces to micro-Newton precision, which revealed significant changes in the mechanics of kismet mutant guts, in terms of elasticity, strain stiffening, and tensile strength. Using 16S rRNA metagenomic sequencing, we also found kismet mutants have reduced diversity of gut microbiota at every taxonomic level and an increase in pathogenic taxa. To investigate the connection between the gut microbiome and behavior, we depleted gut microbiota in kismet mutant and control flies and measured courtship behavior. Depletion of gut microbiota rescued courtship defects of kismet mutant flies, indicating a connection between gut microbiota and behavior. In striking contrast, depletion of gut microbiome in the control strain reduced courtship activity. This result demonstrated that antibiotic treatment can have differential impacts on behavior that may depend on the status of microbial dysbiosis in the gut prior to depletion. We propose that Kismet influences multiple gastrointestinal phenotypes that contribute to the gut-brain axis to influence behavior. Based on our results, we also suggest that gut tissue mechanics should be considered as an element in the gut-brain communication loop, both influenced by and potentially influencing the gut microbiome and neuronal development.