Interaction of intestinal microorganisms with the human host in the framework of autoimmune diseases

Autoimmune diseases, such as systemic lupus erythematosus (SLE), are caused by a complex interaction of environmental-, genetic-, and sex-related factors. Although SLE has traditionally been considered independent from the microbiota, recent work published during the last 5 years suggests a strong connection between SLE and the composition of our gut commensals as one of the main environmental factors linked to this disease. Preliminary data have evidenced that (i) interaction of certain microbial-derived molecules with specific cell receptors and (ii) the influence of certain commensal microorganisms over specific immune cell subsets plays an important role in the pathogenesis of SLE and SLE-like diseases. In addition, epigenetic changes driven by certain microbial groups have been recently proposed as an additional link between gut microbiota and SLE. As immune responses elicited against commensal bacteria are deeply dependent on the composition of the latter, and as microbial populations can be modified by dietary interventions, identifying the precise gut microorganisms responsible for worsening the SLE symptoms is of crucial importance for this and other SLE-related diseases, including antiphospholipid syndrome or lupus nephritis. In this minireview, the current knowledge on the relationships between microbes and SLE and SLE-related diseases is compiled and discussed.This research was funded by Grants AGL2013-44039-R and AGL2010-14952 from the Spanish “Plan Estatal de I + D + I”. BS and AH were recipients of a Ramón y Cajal postdoctoral contract and a FPI grant, respectively, from the Spanish Ministry of Economy and Competitiveness.Peer Reviewe

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.This work was funded by Biopolis SL within the framework of the e-CENIT Project SENIFOOD from the Spanish Ministry of Science and Innovation.Peer Reviewe

Diet: Cause or consequence of the microbial profile of cholelithiasis disease?

Recent dietary habits and lifestyle could explain the shaping of the gut microbiota composition and, in consequence, the increasing prevalence of certain pathologies. However, little attention has been paid to the influence of diet on microbiotas, other than the gut microbiota. This is important in cholelithiasis, given that changes in the production of bile acids may affect gallbladder microbial communities. Our aim was to assess the association between regular dietary intake and gallbladder microbial composition. Fourteen adults with cholelithiasis and 14 controls, sex-age-matched and without gastrointestinal pathology, were included. Diet was assessed through a food frequency questionnaire and quantification of gallbladder microbiota sequences by Illumina 16S rRNA gene-based analysis. The cholelithiasic patients showed greater intake of potatoes and lower consumption of vegetables, non-alcoholic drinks, and sauces, which resulted in a lower intake of energy, lipids, digestible polysaccharides, folate, calcium, magnesium, vitamin C, and some phenolic compounds. Regarding the altered bile microorganisms in cholelithiasic patients, dairy product intake was negatively associated with the proportions of Bacteroidaceae and Bacteroides, and several types of fiber, phenolics, and fatty acids were linked to the abundance of Bacteroidaceae, Chitinophagaceae, Propionibacteraceae, Bacteroides, and Escherichia-Shigella. These results support a link between diet, biliary microbiota, and cholelithiasis.This research was funded by the Spanish “Plan Estatal de I+D+i” Grant number (AGL2013-44761-P) I. Gutiérrez-Díaz was supported by “Plan Regional de Investigación del Principado de Asturias” Grant number (GRUPIN14-043).Peer reviewe

Intestinal dysbiosis is associated with altered short-chain fatty acids and serum-free fatty acids in systemic lupus erythematosus

Metabolic impairments are a frequent hallmark of systemic lupus erythematosus (SLE). Increased serum levels of free fatty acids (FFA) are commonly found in these patients, although the underlying causes remain elusive. Recently, it has been suggested that factors other than inflammation or clinical features may be involved. The gut microbiota is known to influence the host metabolism, the production of short-chain fatty acids (SCFA) playing a potential role. Taking into account that lupus patients exhibit an intestinal dysbiosis, we wondered whether altered FFA levels may be associated with the intestinal microbial composition in lupus patients. To this aim, total and specific serum FFA levels, fecal SCFA levels, and gut microbiota composition were determined in 21 SLE patients and 25 healthy individuals. The Firmicutes to Bacteroidetes (F/B) ratio was strongly associated with serum FFA levels in healthy controls (HC), even after controlling for confounders. However, this association was not found in lupus patients, where a decreased F/B ratio and increased FFA serum levels were noted. An altered production of SCFA was related to the intestinal dysbiosis in lupus, while SCFA levels paralleled those of serum FFA in HC. Although a different serum FFA profile was not found in SLE, specific FFA showed distinct patterns on a principal component analysis. Immunomodulatory omega-3 FFA were positively correlated to the F/B ratio in HC, but not in SLE. Furthermore, divergent associations were observed for pro- and anti-inflammatory FFA with endothelial activation biomarkers in lupus patients. Overall, these findings support a link between the gut microbial ecology and the host metabolism in the pathological framework of SLE. A potential link between intestinal dysbiosis and surrogate markers of endothelial activation in lupus patients is supported, FFA species having a pivotal role.This work was funded through the grants GRUPIN14-043 “Microbiota Humana, Alimentación y Salud” from the “Plan Regional de Investigación del Principado de Asturias” and cofounded from European Union FEDER funds, AGL2010-14952 from the Spanish Ministry of Science and Innovation, and PI012/00523 from the “Fondo de Investigaciones Sanitarias, Instituto de Investigación Carlos III.” JR-C is supported by a contract from the grant GRUPIN14-043.Peer reviewedPeer Reviewe

Different intestinal microbial profile in Over-Weight and obese subjects consuming a diet with low content of fiber and antioxidants

Obesity has been related to an increased risk of multiple diseases in which oxidative stress and inflammation play a role. Gut microbiota has emerged as a mediator in this interaction, providing new mechanistic insights at the interface between fat metabolism dysregulation and obesity development. Our aim was to analyze the interrelationship among obesity, diet, oxidative stress, inflammation and the intestinal microbiota in 68 healthy adults (29.4% normal-weight). Diet was assessed through a food frequency questionnaire and converted into nutrients and dietary compounds using food composition tables. The intestinal microbiota was assessed by quantitative PCR, fecal short chain fatty acids by gas chromatography and serum biomarkers by standard protocols. Higher levels of malondialdehyde (MDA), C reactive protein (CRP), serum leptin, glucose, fat percentage and the intestinal Lactobacillus group were found in the obese people. Cluster analysis of body mass index, fat mass, glucose, LDL/HDL ratio, leptin, MDA and CRP classified the subjects into two groups. The levels of the intestinal Bacteroides-Prevotella-Porphyromonas group were lower in the cluster and linked to a higher pro-oxidant and pro-inflammatory status, whose individuals also had lower intake of fruits, dried fruits, and fish. These results could be useful for designing strategies targeted to obesity prevention

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

Computer Vision and Metrics Learning for Hypothesis Testing: An Application of Q-Q Plot for Normality Test

This paper proposes a new procedure to construct test statistics for hypothesis testing by computer vision and metrics learning. The application highlighted in this paper is applying computer vision on Q-Q plot to construct a new test statistic for normality test. Traditionally, there are two families of approaches for verifying the probability distribution of a random variable. Researchers either subjectively assess the Q-Q plot or objectively use a mathematical formula, such as Kolmogorov-Smirnov test, to formally conduct a normality test. Graphical assessment by human beings is not rigorous whereas normality test statistics may not be accurate enough when the uniformly most powerful test does not exist. It may take tens of years for statistician to develop a new and more powerful test statistic. The first step of the proposed method is to apply computer vision techniques, such as pre-trained ResNet, to convert a Q-Q plot into a numerical vector. Next step is to apply metric learning to find an appropriate distance function between a Q-Q plot and the centroid of all Q-Q plots under the null hypothesis, which assumes the target variable is normally distributed. This distance metric is the new test statistic for normality test. Our experimentation results show that the machine-learning-based test statistics can outperform traditional normality tests in all cases, particularly when the sample size is small. This study provides convincing evidence that the proposed method could objectively create a powerful test statistic based on Q-Q plots and this method could be modified to construct many more powerful test statistics for other applications in the future

Intestinal dysbiosis associated with systemic lupus erythematosus

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

Microbiota modulation by diet in humans: prebiotics, fibres and other compounds

Based on the relevance of the intestinal microbiota on health, this article is focused on the effect of diet, and its components on modulating the activity of the colonic flora. There are evidences regarding the effects of different prebiotics, as fructo-oligosaccharides (FOS), galact-oligosaccharides (GOS), inulin and resistant starch, on the microbiota modulation and some of its metabolites. In addition, it will be highlighted the importance of other compounds associated with fibre intake, as polyphenols, whose prebiotic/antimicrobial effects remains to be elucidated. Future studies analysing the influence of probiotics and prebiotics on the microbial populations should include a detailed polyphenol intake.Peer Reviewe

Diet and Microbiome in Health and Aging

After several years of research, sufficient evidence has been found supporting that diet is one of the main factors able to modulate both composition and activity of the intestinal microbiota, thus positioning it as a cornerstone in the host-microbiota interface. The gut microbiota plays a crucial role in the maintenance of normal host physiology. The rapid development of next-generation sequencing methods for nucleic acids, in the last decade, has facilitated in-depth studies of gut microbiome composition and function. The articles collected in this Special Issue of Nutrients journal are intended to contribute to the progress of knowledge in the field as well as the basis for putative dietary interventions aimed at counteracting microbiota dysbiosis. These novel papers deal with the study of the relationship of diet on the intestinal microbiota from the early stages of life, deepening in certain pathologies, particularly relevant in this period of life, such as allergies, autism or overweight, up to adulthood and senescence. In addition, comprehensive review papers on hot topics such as the gut-brain axis, or the potential benefits of probiotics and prebiotics in the diet for allergy modulation were included. By providing updated and contrasted data, the authors propose several hypotheses that will be addressed in future research, which will undoubtedly arouse the interest of Nutrients journal readers. The correct establishment of the gut microbiota at early life is known to be a milestone process for the later health of humans. Exponential studies during the last years have correlated aberrant gut microbiota colonization at the beginning of life with impairment on the intestinal, immune or nervous systems development [1]. Overweight, allergic diseases or neurodevelopmental disorders, like autism spectrum disorder (ASD), have been associated with gut microbiota alterations. Therefore, studying the composition of the gut microbiota at early life to be used as a predictor or to be target for modulation, is of great interest to prevent possible future diseases. In this context, Gonzalez et al. [2] evaluated the link between gut microbes and infant weight gain in the course of the first year of life in a cohort of full-term one-month aged neonates. They found significant associations between specific microbial groups and higher weight at 6 and 12 months, albeit being differently in vaginally and C-section delivered babies. Those gut microbes could be considered as potential microbial predictors for later weight gain