Adriana Cuervo

Intestinal Dysbiosis Associated with Systemic Lupus Erythematosus

ABSTRACT Systemic lupus erythematosus (SLE) is the prototypical systemic autoimmune disease in humans and is characterized by the presence of hyperactive immune cells and aberrant antibody responses to nuclear and cytoplasmic antigens, including characteristic anti–double-stranded DNA antibodies. We performed a cross-sectional study in order to determine if an SLE-associated gut dysbiosis exists in patients without active disease. A group of 20 SLE patients in remission, for which there was strict inclusion and exclusion criteria, was recruited, and we used an optimized Ion Torrent 16S rRNA gene-based analysis protocol to decipher the fecal microbial profiles of these patients and compare them with those of 20 age- and sex-matched healthy control subjects. We found diversity to be comparable based on Shannon’s index. However, we saw a significantly lower Firmicutes/Bacteroidetes ratio in SLE individuals (median ratio, 1.97) than in healthy subjects (median ratio, 4.86; P < 0.002). A lower Firmicutes/Bacteroidetes ratio in SLE individuals was corroborated by quantitative PCR analysis. Notably, a decrease of some Firmicutes families was also detected. This dysbiosis is reflected, based on in silico functional inference, in an overrepresentation of oxidative phosphorylation and glycan utilization pathways in SLE patient microbiota. IMPORTANCE Growing evidence suggests that the gut microbiota might impact symptoms and progression of some autoimmune diseases. However, how and why this microbial community influences SLE remains to be elucidated. This is the first report describing an SLE-associated intestinal dysbiosis, and it contributes to the understanding of the interplay between the intestinal microbiota and the host in autoimmune disorders. Growing evidence suggests that the gut microbiota might impact symptoms and progression of some autoimmune diseases. However, how and why this microbial community influences SLE remains to be elucidated. This is the first report describing an SLE-associated intestinal dysbiosis, and it contributes to the understanding of the interplay between the intestinal microbiota and the host in autoimmune disorders.

Ranking the impact of human health disorders on gut metabolism: Systemic lupus erythematosus and obesity as study cases

Multiple factors have been shown to alter intestinal microbial diversity. It remains to be seen, however, how multiple collective pressures impact the activity in the gut environment and which, if any, is positioned as a dominant driving factor determining the final metabolic outcomes. Here, we describe the results of a metabolome-wide scan of gut microbiota in 18 subjects with systemic lupus erythematosus (SLE) and 17 healthy control subjects and demonstrate a statistically significant difference (p < 0.05) between the two groups. Healthy controls could be categorized (p < 0.05) based on their body mass index (BMI), whereas individuals with SLE could not. We discuss the prevalence of SLE compared with BMI as the dominant factor that regulates gastrointestinal microbial metabolism and provide plausible explanatory causes. Our results uncover novel perspectives with clinical relevance for human biology. In particular, we rank the importance of various pathophysiologies for gut homeostasis.

Fiber from a regular diet is directly associated with fecal short-chain fatty acid concentrations in the elderly

It has recently been suggested that fiber exerts a considerable effect on microbiota composition and on fecal short-chain fatty acid (SCFA) production, the concentration of which in the colon is important for immune regulation and for maintaining gut and overall health. To test the hypothesis that the fiber consumed in a regular diet affects fecal SCFA concentrations in the elderly, the authors investigated the association between different types of fiber intake and fecal SCFA concentrations in 32 institutionalized elderly subjects aged between 76 and 95 years. Food intake was recorded by means of a validated food frequency questionnaire. Total, soluble (pectin and hemicellulose) and insoluble (pectin, hemicellulose, Klason lignin, and cellulose) fiber was determined using Marlett Food Composition Tables. Analysis of acetic, propionic, and butyric acid concentrations was performed using gas chromatography-mass spectrometry. Potato intake was directly associated with SCFA concentrations and apple intake with propionate concentration. Of the fibers, cellulose showed an independent association with acetate and butyrate concentrations, and insoluble pectin explained a part of the variation in propionate. In conclusion, our results provide further evidence regarding the relation between diet and SCFA concentration in the elderly. The identification of an association between the regular intake of foods such as potatoes and the production of SCFAs provides an opportunity to improve public health.

Association of Polyphenols from Oranges and Apples with Specific Intestinal Microorganisms in Systemic Lupus Erythematosus Patients

Our group has recently shown the existence of a gut microbial dysbiosis in systemic lupus erythematosus (SLE), supporting previous evidence involving intestinal bacteria in the initiation and amplification of autoimmune diseases. While several studies have addressed the use of dietary fibres to modify intestinal microbiota, information about other correlated components, such as polyphenols, is scarce. The aim of this work was to identify dietary components able to influence this altered microbiota in 20 SLE women and 20 age-matched controls. Food intake was recorded by means of a food frequency questionnaire. The intake of fibres was calculated from Marlett tables, and Phenol-Explorer was used for polyphenol consumption. Results showed positive associations between flavone intake and Blautia, flavanones and Lactobacillus, and dihydrochalcones and Bifidobacterium in the SLE group. Regarding the controls, dihydroflavonols were directly associated with Faecalibacterium, whereas flavonol intake was inversely associated with Bifidobacterium. From the food sources of these polyphenols related to microbiota, orange intake was directly associated with Lactobacillus and apple with Bifidobacterium in SLE, whilst red wine was the best contributor to Faecalibacterium variation. The association between common foods and particular microbial genera, reported to be decreased in SLE, could be of great importance for these patients.

Allergic Patients with Long-Term Asthma Display Low Levels of Bifidobacterium adolescentis.

Accumulated evidence suggests a relationship between specific allergic processes, such as atopic eczema in children, and an aberrant fecal microbiota. However, little is known about the complete microbiota profile of adult individuals suffering from asthma. We determined the fecal microbiota in 21 adult patients suffering allergic asthma (age 39.43 ± 10.98 years old) and compare it with the fecal microbiota of 22 healthy controls (age 39.29 ± 9.21 years old) using culture independent techniques. An Ion-Torrent 16S rRNA gene-based amplification and sequencing protocol was used to determine the fecal microbiota profile of the individuals. Sequence microbiota analysis showed that the microbial alpha-diversity was not significantly different between healthy and allergic individuals and no clear clustering of the samples was obtained using an unsupervised principal component analysis. However, the analysis of specific bacterial groups allowed us to detect significantly lower levels of bifidobacteria in patients with long-term asthma. Also, in allergic individuals the Bifidobacterium adolescentis species prevailed within the bifidobacterial population. The reduction in the levels on bifidobacteria in patients with long-term asthma suggests a new target in allergy research and opens possibilities for the therapeutic modulation of the gut microbiota in this group of patients.

Pilot Study of Diet and Microbiota: Interactive Associations of Fibers and Polyphenols with Human Intestinal Bacteria

Several studies have addressed the use of dietary fibers in the modulation of intestinal microbiota; however, information about other highly correlated components in foods, such as polyphenols, is scarce. The aim of this work was to explore the association between the intake of fibers and polyphenols from a regular diet and fecal microbiota composition in 38 healthy adults. Food intake was recorded using an annual food frequency questionnaire (FFQ). Quantification of microbial populations in feces was performed by quantitative PCR. A negative association was found between the intake of pectins and flavanones from oranges and the levels of Blautia coccoides and Clostridium leptum. By contrast, white bread, providing hemicellulose and resistant starch, was directly associated with Lactobacillus. Because some effects on intestinal microbiota attributed to isolated fibers or polyphenols might be modified by other components present in the same food, future research should be focused on diet rather than individual compounds.

Microbial Targets for the Development of Functional Foods Accordingly with Nutritional and Immune Parameters Altered in the Elderly

Objective: The development of functional foods for microbiota modulation in the elderly constitutes an interesting strategy. However, for such development, specific targets, not just in terms of microbiota but also considering immune and nutritional parameters, should be identified in this population. Methods: We analyzed the intestinal microbiota and immune parameters in 38 institutionalized elderly (mean 84 years old) and a group of 38 elderly adults (mean 62 years old). Nutritional assessments were also carried out. Results: The elderly people in this study presented reduced levels of Faecalibacterium genus and Bacteroides and Blautia coccoides groups and increased Lactobacillus group, as well as reduced levels of fecal short-chain fatty acids (SCFA) when compared to younger adults. Moreover, they showed higher levels of the proinflammatory cytokines tumor necrosis factor (TNF)-α and interleukin (IL)-12 as well as the chemokine IL-8. Significant nutritional deficiencies were also observed in the elderly group. Conclusion: The results obtained in this study suggest potential targets for the development of functional foods for the elderly population.

Red wine consumption is associated with fecal microbiota and malondialdehyde in a human population.

Objectives: Red wine intake has been associated with a lower risk of cardiovascular disease; its polyphenol content is the primary cause of antioxidant and anti-inflammatory properties attributed to this beverage. However, the way in which these activities are exerted is not yet clear, although some authors have proposed that intestinal microbiota could be implicated. Methods: The association between red wine intake, inflammation, and oxidative stress parameters and fecal microbial populations has been explored in 38 adult volunteers. Food intake was recorded by means of an annual food frequency questionnaire (FFQ). Energy, cholesterol, and ethanol intake were analyzed using the nutrient Food Composition Tables developed by Centro de Enseñanza Superior de Nutrición y Dietética (CESNID) and polyphenol intake was obtained from the Phenol-Explorer Database. Fecal levels of Akkermansia, Bacteroides, Bifidobacterium, Blautia coccoides group, Clostridium leptum group, Lactobacillus group, and Faecalibacterium prausnitzii were determined by quantitative polymerase chain reaction. Serum concentrations of C-reactive protein (CRP), malondialdehyde (MDA), total antioxidant capacity (TAC), cholesterol, triglycerides and glucose were analyzed by standard methods. Results: Subjects with regular consumption of red wine (mean = 100 ml/day) had lower serum concentrations of MDA and lower fecal levels of B. coccoides, C. leptum, Bifidobacterium, and Lactobacillus. A positive association between MDA levels and B. coccoides and Lactobacillus was also found. Conclusion: Regular consumption of red wine appears to be associated with a reduced serum lipoperoxidation in which the intestinal microbiota may be involved.

Fatty acids intake and immune parameters in the elderly

INTRODUCTION The rapid increase on life-expectancy represents a major challenge and economic burden for modern societies. Several studies have focused on the effects of polyunsaturated fatty acids (PUFA) upon the immune system; however less attention has been paid to the effects of monounsaturated fatty acids (MUFA). In this work we investigated the relationship of habitual consumption of different types of fatty acids with different immune parameters in the elderly. SUBJECTS AND METHODS 40 institutionalized elderly (76-95 y) and 35 home-living middle-age subjects (57-65 y) were recruited. Dietary intakes of macronutrients, fiber and fatty acids, as well as immune parameters such as serum cytokines levels (IL-10, TNF-α, IL-8, IL-17, TGF-β and IL-12), phagocytic activity and cytotoxic NK activity, were determined. RESULTS Elderly subjects had a lower intake of total lipids. MUFA intake was significantly lower in the elderly group than in middle-age adults whilst the contrary was true for PUFA. MUFA intake in the elderly was found to be positively associated with IL-12 (β = 0.879) and TNF-α (β = 0.789) serum concentrations, whilst PUFA intake was inversely related to levels of IL-12 (β = -0.534). These associations were not observed in the middle-age group. CONCLUSION MUFA intake may contribute to the pro-inflammatory status present in the elderly. It may be advisable to develop future nutrient recommendations specific for elderly taking into account immune parameters.

Polyphenol Intake in Elderly People Is Associated with Lipid Oxidative Damage

Objective: We hypothesized an association between physiological amounts of different classes and subclasses of polyphenol from a subjects regular diet and lipid peroxidation. Subjects and Methods: Diet was assessed through direct observation and a semiquantitative food frequency questionnaire. Daily polyphenol intake, total as well as subgroups, and plasma malondialdehyde (MDA) were determined together with other variables used as covariates (age, sex, energy intake, Quetelet index, plasma glucose, cholesterol and triglycerides, and tobacco use) in 159 institutionalized elderly subjects (68 men, 91 women) with a mean age of 73.1 years. Results: Flavonoid intake was inversely associated with MDA in a multiple regression analysis. The potential effect of flavonoids was mainly ascribed to flavanols. A diet score based on the 5 dietary components previously identified as the major contributors to the intake of flavanols was developed. None of the food components was associated with MDA individually, but the overall diet score was inversely associated in a logistic regression analysis. Conclusions: This study represents one of the few attempts to date to evaluate the impact of phenol intake on oxidative damage. Flavonoids intake must be promoted to reduce the negative health effects of oxidative stress in elderly people.