Gut microbiota, its evolutive dynamics and influence on host through its protective, trophic and metabolic actions, has a key role in health and opens unique opportunities for the identification of ...new markers of the physiopathological state of each individual. Alterations in gut microbiota composition have been associated with plenty disorders. Of interest, the vast number of studies demonstrates the role of microbiota in obesity, a serious public health problem that has reached epidemic proportions in many developed and middle-income countries. The economic and health costs of this condition and its comorbidities such as fatty liver, insulin resistance/diabetes, or cardiovascular events are considerable. Therefore, every strategy designed to reduce obesity would imply important savings. Targeting microbiota, in order to restore/modulate the microbiota composition with antibiotics, probiotics, prebiotics, or even fecal transplants, is considered as a promising strategy for the development of new solutions for the treatment of obesity. However, there is still lot to do in this field in order to identify the exact composition of microbiota in “health” and the specific mechanisms that regulate the host-microbiotal crosstalk. In addition, it is important to note that changes not only in the gut microbiota profile (abundance) but also in its metabolism and functions need to be taken into account in the context of contribution in the physiopathology of obesity and related disorders.
Abstract
Background
Whether human immunodeficiency virus (HIV) infection impacts gut microbial α-diversity is controversial. We reanalyzed raw 16S ribosomal RNA (rRNA) gene sequences and metadata ...from published studies to examine α-diversity measures between HIV-uninfected (HIV–) and HIV-infected (HIV+) individuals.
Methods
We conducted a systematic review and individual level meta-analysis by searching Embase, Medline, and Scopus for original research studies (inception to 31 December 2017). Included studies reported 16S rRNA gene sequences of fecal samples from HIV+ patients. Raw sequence reads and metadata were obtained from public databases or from study authors. Raw reads were processed through standardized pipelines with use of a high-resolution taxonomic classifier. The χ2 test, paired t tests, and generalized linear mixed models were used to relate α-diversity measures and clinical metadata.
Results
Twenty-two studies were identified with 17 datasets available for analysis, yielding 1032 samples (311 HIV–, 721 HIV+). HIV status was associated with a decrease in measures of α-diversity (P < .001). However, in stratified analysis, HIV status was associated with decreased α-diversity only in women and in men who have sex with women (MSW) but not in men who have sex with men (MSM). In analyses limited to women and MSW, controlling for HIV status, women displayed increased α-diversity compared with MSW.
Conclusions
Our study suggests that HIV status, sexual risk category, and gender impact gut microbial community α-diversity. Future studies should consider MSM status in gut microbiome analyses.
Gut microbial α-diversity decreases in HIV+ compared with HIV– women and men who have sex with women (MSW), but not in men who have sex with men. Women have increased α-diversity as compared to MSW.
The aim of this study was to examine the effects of α-lipoic acid (α-LA) on liver mitochondrial bioenergetics and oxidative status for 8 weeks in normal-healthy animals. A pair-fed group was included ...to differentiate between α-LA direct effects and those changes due to reduced food intake. α-LA decreased body weight gain, liver weight and insulin levels with no differences compared to its pair-fed group. α-LA significantly reduced energy efficiency, the activity of the electron transport chain complexes and induced a lower efficiency of oxidative phosphorylation with reduced ATP production. α-LA supplementation directly decreased plasma triglycerides (TGs), free fatty acids and ketone bodies levels. A significant reduction in hepatic TG content was also observed. A significant up-regulation of Cpt1a, Acadl and Sirt3, all β-oxidation genes, along with a significant deacetylation of the forkhead transcription factor 3a (FOXO3A) was found in α-LA-treated animals. Thus, α-LA along with a standard chow diet has direct actions on lipid metabolism and liver by modulating mitochondrial function in normal-weight rats. These results should be taken into account when α-LA is administered or recommended to a healthy population.
Resveratrol is beneficial in obese and diabetic rodents. However, its low bioavailability raises questions about its therapeutic relevance for treating or preventing obesity complications. In this ...context, many related natural polyphenols are being tested for their putative antidiabetic and anti-obesity effects. This prompted us to study the influence of piceatannol, a polyhydroxylated stilbene, on the prevention of obesity complications in Zucker obese rats. A 6-week supplementation was followed by the determination of various markers in plasma, liver, adipose tissue and heart, together with a large-scale analysis of gut microbiota composition. When given in doses of 15 or 45 mg/kg body weight/day, piceatannol did not reduce either hyperphagia or fat accumulation. It did not modify the profusion of the most abundant phyla in gut, though slight changes were observed in the abundance of several
Lactobacillus
,
Clostridium
, and
Bacteroides
species belonging to
Firmicutes
and
Bacteroidetes
. This was accompanied by a tendency to reduce plasma lipopolysaccharides by 30 %, and by a decrease of circulating non-esterified fatty acids, LDL-cholesterol, and lactate. While piceatannol tended to improve lipid handling, it did not mitigate hyperinsulinemia and cardiac hypertrophy. However, it increased cardiac expression of ephrin-B1, a membrane protein that contributes to maintaining cardiomyocyte architecture. Lastly, ascorbyl radical plasma levels and hydrogen peroxide release by adipose tissue were similar in control and treated groups. Thus, piceatannol did not exhibit strong slimming capacities but did limit several obesity complications.
The association between gut microbiota and animal models of multiple sclerosis has been well established; however, studies in humans are scarce.
We performed a descriptive, cross-sectional study ...comparing the relative composition of gut microbiota in 30 patients with multiple sclerosis (15 treated with interferon β-1b, 15 not receiving this treatment) and 14 healthy controls using next generation sequencing.
Patients with multiple sclerosis and controls showed differences in the proportion of Euryarchaeota, Firmicutes, Proteobacteria, Actinobacteria, and Lentisphaerae phyla and in 17 bacterial species. More specifically, we found significant differences in the proportion of Firmicutes, Actinobacteria, and Lentisphaerae and 6 bacteria species between controls and untreated patients; however, these differences disappeared when compared with treated patients. Untreated patients showed a significant reduction in the proportion of Prevotella copri compared to controls, while the bacteria was significantly more abundant in patients treated with interferon β-1b than in untreated patients, with levels resembling those observed in the healthy control group.
We observed differences in gut microbiota composition between patients with multiple sclerosis and controls, and between patients treated and not treated with interferon β-1b. In most cases, no differences were observed between treated patients and healthy controls, particularly for P. copri levels. This suggests that the clinical improvements observed in patients with multiple sclerosis receiving interferon β-1b may result from the effect of the drug on gut microbiota. Longitudinal and functional studies are necessary to establish a causal relationship.
El papel de la microbiota en los modelos animales de esclerosis múltiple está bien establecido; por el contrario, los estudios en humanos son escasos.
Estudio transversal descriptivo que compara la composición relativa de la microbiota intestinal en 30 pacientes con esclerosis múltiple (15 tratados con interferón β-1b, 15 sin tratamiento) y 14 controles sanos utilizando la secuenciación de última generación.
Los sujetos control y los pacientes con esclerosis múltiple presentaron diferente abundancia de los filos Euryarchaeota, Firmicutes, Proteobacteria, Actinobacteria, y Lentisphaerae y 17 especies bacterianas. Concretamente, la abundancia en Firmicutes, Actinobacteria y Lentisphaerae y 6 especies mostró diferencias al comparar los grupos control y sin tratamiento, desapareciendo esta diferencia cuando se compararon con los pacientes tratados. Se observó reducción estadísticamente significativa en la abundancia de Prevotella copri en pacientes sin tratamiento en comparación con controles, mientras que los tratados con interferón β-1b presentaron un aumento significativo frente a pacientes sin tratamiento, asemejándose al grupo de pacientes sanos control.
La composición de la microbiota intestinal fue diferente entre los pacientes con esclerosis múltiple y los controles, y entre los pacientes sin tratamiento y los tratados con interferón β-1b. En la mayoría de los casos, no se encontraron diferencias entre los pacientes tratados y los controles sanos, siendo especialmente evidente con P. copri. Esto podría indicar que la influencia del interferón β-1b sobre la microbiota intestinal podría subyacer en los beneficios clínicos observados en pacientes con esclerosis múltiple que siguen este tratamiento. Serán necesarios estudios longitudinales y funcionales para poder mostrar causalidad.
Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the general population. The NAFLD spectrum ranges from simple steatosis to cirrhosis. The chemokine ...CCL5/RANTES plays an important role in the progression of hepatic inflammation and fibrosis. The objective of this study was to examine the effects of maraviroc, a CCR5 antagonist, on liver pathology in a NAFLD mouse model.
A total of 32 male C57BL/6 mice were randomly assigned to one of four groups: (i) control group (chow diet plus tap water); (ii) maraviroc group (chow diet plus maraviroc in drinking water); (iii) high-fat diet (HFD) group (HFD plus tap water); and (iv) maraviroc/HFD group (HFD plus maraviroc). All mice were sacrificed 16 weeks after the beginning of the experiment. Biochemical analyses and liver examinations were performed.
Mice in the HFD group showed a tendency towards increased body mass gain and liver damage compared with the maraviroc/HFD group. Moreover, liver weight in the HFD group was significantly higher than in the maraviroc/HFD group. Hepatic triglyceride concentration in the maraviroc/HFD group was significantly lower than in the HFD group. Interestingly, the maraviroc/HFD group exhibited a lower degree of steatosis. Furthermore, hepatic CCL5/RANTES expression was significantly lower in the maraviroc/HFD group than in the HFD group. Overall, no differences were observed between the control group and the maraviroc group.
Maraviroc ameliorates hepatic steatosis in an experimental model of NAFLD.
Several studies have suggested that oxidative stress might cause and aggravate the inflammatory state associated with obesity and could be the link between excessive weight gain and its related ...disorders such as insulin resistance and cardiovascular diseases. Thus, antioxidant treatment has been proposed as a therapy to prevent and manage obesity and associated complications. Therefore, the aim of the present study was to investigate the effects of supplementation of a standard or high fat diet with the antioxidant lipoic acid (LA) during 56 days, on body weight gain, adiposity, feed efficiency and intestinal sugar absorption, in male Wistar rats. LA supplementation induced a lower body weight gain and adipose tissue size in both control or high fat fed rats accompanied by a reduction in food intake. The group fed on a high fat diet and treated with LA (OLIP group) showed a lower body weight gain than its corresponding Pair-Fed (PF) group (
P<0.05
), which received the same amount of food than LA-treated animals but with no LA. In fact, LA induced a reduction on feed efficiency and also significantly decreased intestinal α-methylglucoside (α-MG) absorption both in lean and obese rats. These results suggest that the beneficial effects of dietary supplementation with LA on body weight gain are mediated, at least in part, by the reduction observed in food intake and feed efficiency. Furthemore, the inhibitory action of LA on intestinal sugar transport could explain in part the lower feed efficiency observed in LA-treated animals and therefore, highlighting the beneficial effects of LA on obesity.
Resumen
La enfermedad de Alzheimer (EA) es la forma más común de demencia y tiene una elevada morbilidad y mortalidad. La EA se caracteriza principalmente por la presencia de dos estructuras ...aberrantes en el cerebro de los pacientes, placas seniles formadas por péptido-β-amiloide (Aβ) y ovillos neurofibrilares cuyo principal componente es la proteína tau fosforilada. Aunque actualmente no se conoce bien la etiopatogenia, cada vez son más los estudios que demuestran un efecto causal del microbioma intestinal sobre la EA y las funciones cognitivas, a través del "eje microbiota intestino-cerebro". Las evidencias científicas sugieren un posible efecto protector de los polifenoles del vino frente a los trastornos neurodegenerativos aunque se desconocen los mecanismos y, hasta el momento, los estudios para evaluar de forma exhaustiva el efecto del vino sobre la etiopatogenia de la EA son muy escasos. El objetivo principal de la línea de investigación que enmarca este trabajo es entender cómo la dieta, y especialmente los polifenoles presentes en los alimentos vegetales, y otros factores del estilo de vida interactúan con el microbioma oral e intestinal, en relación con la salud digestiva y el deterioro cognitivo. Para ello, se está llevando a cabo una aproximación experimental que tiene como finalidad evaluar el posible efecto protector de los polifenoles del vino, mediante la suplementación de la dieta en dos modelos murinos de la EA (patología Aß y Tau), y, por otro lado, se está profundizando en el estudio de los mecanismos de protección mediante la evaluación de los efectos del ácido protocatéquico sobre la actividad eléctrica del cerebro.
Alzheimer's disease (AD) is the most common form of age-related dementia with high morbidity and mortality. AD is mainly characterized by the presence of two aberrant structures in the brain of patients, senile plaques formed by peptide-β-amyloid (Aβ) and neurofibrillary tangles whose main component is phosphorylated tau protein. Although the etiopathogenesis is currently not well understood, an increasing number of studies demonstrate a causal effect of the gut microbiome on AD and cognitive functions, through the "gut-brain microbiota axis". Scientific evidence suggests a possible protective effect of wine polyphenols against neurodegenerative disorders although the mechanisms are unknown and, so far, studies to evaluate comprehensively the effect of wine on the etiopathogenesis of AD are very scarce. The main objective of the research line that frames this work is to understand how diet, and especially the polyphenols present in plant foods, and other lifestyle factors interact with the oral and intestinal microbiome in relation to digestive health and cognitive impairment. To this end, an experimental approach is being carried out to evaluate the possible protective effect of wine polyphenols through dietary supplementation in two murine models of AD (Aß and Tau pathology), and, on the other hand, the study of the protective mechanisms is being deepened by evaluating the effects of protocatechuic acid on the electrical activity of the brain.
El papel de la microbiota en los modelos animales de esclerosis múltiple está bien establecido; por el contrario, los estudios en humanos son escasos.
Estudio transversal descriptivo que compara la ...composición relativa de la microbiota intestinal en 30 pacientes con esclerosis múltiple (15 tratados con interferónβ-1b, 15 sin tratamiento) y 14 controles sanos utilizando la secuenciación de última generación.
Los sujetos control y los pacientes con esclerosis múltiple presentaron diferente abundancia de los filos Euryarchaeota, Firmicutes, Proteobacteria, Actinobacteria, y Lentisphaerae y 17 especies bacterianas. Concretamente, la abundancia en Firmicutes, Actinobacteria y Lentisphaerae y 6 especies mostró diferencias al comparar los grupos control y sin tratamiento, desapareciendo esta diferencia cuando se compararon con los pacientes tratados. Se observó reducción estadísticamente significativa en la abundancia de Prevotella copri en pacientes sin tratamiento en comparación con controles, mientras que los tratados con interferónβ-1b presentaron un aumento significativo frente a pacientes sin tratamiento, asemejándose al grupo de pacientes sanos control.
La composición de la microbiota intestinal fue diferente entre los pacientes con esclerosis múltiple y los controles, y entre los pacientes sin tratamiento y los tratados con interferónβ-1b. En la mayoría de los casos, no se encontraron diferencias entre los pacientes tratados y los controles sanos, siendo especialmente evidente con P. copri. Esto podría indicar que la influencia del interferónβ-1b sobre la microbiota intestinal podría subyacer en los beneficios clínicos observados en pacientes con esclerosis múltiple que siguen este tratamiento. Serán necesarios estudios longitudinales y funcionales para poder mostrar causalidad.
The association between gut microbiota and animal models of multiple sclerosis has been well established; however, studies in humans are scarce.
We performed a descriptive, cross-sectional study comparing the relative composition of gut microbiota in 30 patients with multiple sclerosis (15 treated with interferon β–1b, 15 not receiving this treatment) and 14 healthy controls using next generation sequencing.
Patients with multiple sclerosis and controls showed differences in the proportion of Euryarchaeota, Firmicutes, Proteobacteria, Actinobacteria, and Lentisphaerae phyla and in 17 bacterial species. More specifically, we found significant differences in the proportion of Firmicutes, Actinobacteria, and Lentisphaerae and 6 bacteria species between controls and untreated patients; however, these differences disappeared when compared with treated patients. Untreated patients showed a significant reduction in the proportion of Prevotella copri compared to controls, while the bacteria was significantly more abundant in patients treated with interferon β–1b than in untreated patients, with levels resembling those observed in the healthy control group.
We observed differences in gut microbiota composition between patients with multiple sclerosis and controls, and between patients treated and not treated with interferon β–1b. In most cases, no differences were observed between treated patients and healthy controls, particularly for P. copri levels. This suggests that the clinical improvements observed in patients with multiple sclerosis receiving interferon β–1b may result from the effect of the drug on gut microbiota. Longitudinal and functional studies are necessary to establish a causal relationship.
Obesity rates have dramatically increased over the last few decades and, at the same time, major changes in the type of fatty acid intake have occurred. Linoleic acid, an n‐6 polyunsaturated fatty ...acid, is an essential fatty acid occurring in high amounts in several western diets. A potential role of this fatty acid on obesity has been suggested. Controversial effects of linoleic acid on insulin sensitivity have also been reported. Thus, the aim of this study was to examine the direct effects of linoleic acid on leptin and adiponectin production, two adipokines known to influence weight gain and insulin sensitivity. Because insulin‐stimulated glucose metabolism is an important regulator of leptin production, the effects of linoleic acid on adipocyte metabolism were also examined. For this purpose, isolated rat adipocytes were incubated with linoleic acid (1–200 μM) in the absence or presence of insulin. Linoleic acid (1–200 μM) significantly decreased insulin‐stimulated leptin secretion and expression (P < 0.05), however, no changes in basal leptin production were observed. Linoleic acid also induced a significant decrease (~20%) in adiponectin secretion (P < 0.05), but only in the presence of insulin and at the highest concentration tested (200 μM). This fatty acid did not modify either glucose uptake or lactate production and the percentage of glucose metabolized to lactate was not changed either. Together, these results suggest that linoleic acid seems to interfere with other insulin signalling pathway different from those controlling glucose uptake and metabolism, but involved in the regulation of leptin and adiponectin production.
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