Role of antioxidative activity in the docosahexaenoic acid's enteroprotective effect in the indomethacin-induced small intestinal injury model.

Therapeutic effect of non-steroidal anti-inflammatory drugs (NSAIDs) has been related with gastrointestinal injury. Docosahexaenoic acid (DHA), an omega-3 polyunsaturated fatty acid (PUFA), can prevent gastric and small intestinal damage. Nonetheless, contribution of antioxidative action in the protective effect of DHA has not been evaluated before in the small intestine injury after indomethacin treatment. Pathogenesis of NSAID-induced small intestinal injury is multifactorial, and reactive oxidative species have been related to indomethacin's small intestinal damage. The present work aimed to evaluate antioxidative activity in the protective action of DHA in the indomethacin-induced small intestinal damage. Female Wistar rats were gavage with DHA (3 mg/kg) or omeprazole (3 mg/kg) for 10 days. Each rat received indomethacin (3 mg/kg, orally) daily to induce small intestinal damage. The total area of intestinal ulcers and histopathological analysis were performed. In DHA-treated rats, myeloperoxidase and superoxide dismutase activity, glutathione, malondialdehyde, leukotriene, and lipopolysaccharide (LPS) levels were measured. Furthermore, the relative abundance of selective bacteria was assessed. DHA administration (3 mg/kg, p.o.) caused a significant decrease in indomethacin-induced small intestinal injury in Wistar rats after 10 days of treatment. DHA's enteroprotection resulted from the prevention of an increase in myeloperoxidase activity, and lipoperoxidation, as well as an improvement in the antioxidant defenses, such as glutathione levels and superoxide dismutase activity in the small intestine. Furthermore, we showed that DHA's enteroprotective effect decreased significantly LPS levels in indomethacin-induced injury in small intestine. Our data suggest that DHA's enteroprotective might be attributed to the prevention of oxidative stress.

Atrophic astrocytes in aged marmosets present tau hyperphosphorylation, RNA oxidation, and DNA fragmentation.

Astrocytes perform multiple essential functions in the brain showing morphological changes. Hypertrophic astrocytes are commonly observed in cognitively healthy aged animals, implying a functional defense mechanism without losing neuronal support. In neurodegenerative diseases, astrocytes show morphological alterations, such as decreased process length and reduced number of branch points, known as astroglial atrophy, with detrimental effects on neuronal cells. The common marmoset (Callithrix jacchus) is a non-human primate that, with age, develops several features that resemble neurodegeneration. In this study, we characterize the morphological alterations in astrocytes of adolescent (mean 1.75 y), adult (mean 5.33 y), old (mean 11.25 y), and aged (mean 16.83 y) male marmosets. We observed a significantly reduced arborization in astrocytes of aged marmosets compared to younger animals in the hippocampus and entorhinal cortex. These astrocytes also show oxidative damage to RNA and increased nuclear plaques in the cortex and tau hyperphosphorylation (AT100). Astrocytes lacking S100A10 protein show a more severe atrophy and DNA fragmentation. Our results demonstrate the presence of atrophic astrocytes in the brains of aged marmosets.

The common marmoset as a model of neurodegeneration.

Human life expectancy has increased over the past few centuries, and the incidence of dementia in the older population is also projected to continue to rise. Neurodegenerative diseases are complex multifactorial conditions for which no effective treatments are currently available. Animal models are necessary to understand the causes and progression of neurodegeneration. Nonhuman primates (NHPs) offer significant advantages for the study of neurodegenerative disease. Among them, the common marmoset, Callithrix jacchus, stands out due to its easy handling, complex brain architecture, and occurrence of spontaneous beta-amyloid (Aß) and phosphorylated tau aggregates with aging. Furthermore, marmosets present physiological adaptations and metabolic alterations associated with the increased risk of dementia in humans. In this review, we discuss the current literature on the use of marmosets as a model of aging and neurodegeneration. We highlight aspects of marmoset physiology associated with aging, such as metabolic alterations, which may help understand their vulnerability to developing a neurodegenerative phenotype that goes beyond normal aging.

The Gut Microbiota-Brain Axis during Aging, Mild Cognitive Impairment and Dementia: Role of Tau Protein, ß-Amyloid and LPS in Serum and Curli Protein in Stool.

Currently, there is an increasing number of people with mild cognitive (MCI) impairment and dementia (D). In the present work we studied the role of tau protein, ß-amyloid, LPS (lipopolysaccharide), and curli protein of elderly adults with MCI or D and the contribution of gut microbiota. Four groups were studied: young subjects, healthy adults older than 60 years (A), elderly adults with MCI (MCI), and elderly adults with dementia (D). A preclinical study was conducted in old male Wistar rats to evaluate the impact of gut microbiota on curli protein abundance in feces and brain. The results showed that with increasing age, tau protein, ß-amyloid, and LPS significantly increased in serum during MCI and D, and this was associated with an increase in the abundance of E. coli that synthesize the amyloid protein curli, that may promote the aggregation of amyloid proteins. Rats showed a clear increase in the abundance of curli protein in the brain during aging. Thus, cognitive impairment and dementia are in part due to an alteration in the gut microbiota-brain axis via increase in curli protein and LPS leading to an increase in tau and ß-amyloid protein.

Dietary Fiber Modulates the Release of Gut Bacterial Products Preventing Cognitive Decline in an Alzheimer's Mouse Model.

Fiber intake is associated with a lower risk for Alzheimer´s disease (AD) in older adults. Intake of plant-based diets rich in soluble fiber promotes the production of short-chain fatty acids (SCFAs: butyrate, acetate, propionate) by gut bacteria. Butyrate administration has antiinflammatory actions, but propionate promotes neuroinflammation. In AD patients, gut microbiota dysbiosis is a common feature even in the prodromal stages of the disease. It is unclear whether the neuroprotective effects of fiber intake rely on gut microbiota modifications and specific actions of SCFAs in brain cells. Here, we show that restoration of the gut microbiota dysbiosis through the intake of soluble fiber resulted in lower propionate and higher butyrate production, reduced astrocyte activation and improved cognitive function in 6-month-old male APP/PS1 mice. The neuroprotective effects were lost in antibiotic-treated mice. Moreover, propionate promoted higher glycolysis and mitochondrial respiration in astrocytes, while butyrate induced a more quiescent metabolism. Therefore, fiber intake neuroprotective action depends on the modulation of butyrate/propionate production by gut bacteria. Our data further support and provide a mechanism to explain the beneficial effects of dietary interventions rich in soluble fiber to prevent dementia and AD. Fiber intake restored the concentration of propionate and butyrate by modulating the composition of gut microbiota in male transgenic (Tg) mice with Alzheimer´s disease. Gut dysbiosis was associated with intestinal damage and high propionate levels in control diet fed-Tg mice. Fiber-rich diet restored intestinal integrity and promoted the abundance of butyrate-producing bacteria. Butyrate concentration was associated with better cognitive performance in fiber-fed Tg mice. A fiber-rich diet may prevent the development of a dysbiotic microbiome and the related cognitive dysfunction in people at risk of developing Alzheimer´s disease.

Aloe vera and Fermented Extracts Exhibit an Anti-Inflammatory Effect on Human Glioblastoma/Astrocytoma U373 MG Cells.

The anti-inflammatory effects of Aloe vera (AV), polysaccharide extract from AV, and extracts from the digestion and colonic fermentation of AV were evaluated using an immortal astrocyte cell line (U373 MG) that develops a neuro-inflammatory profile. Cell viability and inflammatory markers were assessed after stimulation with neuropeptide substance P (SP) that activates the pro-inflammatory MAPK (mitogen-activated protein kinase) pathway. Cell viability after SP treatment was over 50% at 10 mg/mL AV, polysaccharide extract from AV, extracts from the digestion: non-digestible fraction of AV non-digestible fraction of polysaccharide extract from AV and extracts from the colonic fermentation of AV, at 4 and 24 h. Moreover, cells exposed to SP and treated with these extracts showed lower protein-activated ERK1/ERK2 (extracellular signal-regulated kinases 1 and 2), p38 (MAPK protein p38), and NFκB (nuclear factor κB) levels with respect to the SP-stimulated control. Inflammation inhibition by extracts of polysaccharide extract from AV and extracts from the colonic fermentation of AV, at 24 h in the study of p38 was not as statistically significant in ERK1/ERK2 and NFκB. Nevertheless, there was a significant decrease (p < 0.05) in pro-inflammatory cytokine IL-6 levels in cells exposed to all samples. Samples with extracts from the colonic fermentation of AV, at 4 or 24 h showed the highest inhibitory effect on IL-6 production.

Dissecting the copper bioinorganic chemistry of the functional and pathological roles of the prion protein: Relevance in Alzheimer's disease and cancer.

The cellular prion protein (PrPC) is a metal-binding biomolecule that can interact with different protein partners involved in pivotal physiological processes, such as neurogenesis and neuronal plasticity. Recent studies profile copper and PrPC as important players in the pathological mechanisms of Alzheimer's disease and cancer. Although the copper-PrPC interaction has been characterized extensively, the role of the metal ion in the physiological and pathological roles of PrPC has been barely explored. In this article, we discuss how copper binding and proteolytic processing may impact the ability of PrPC to recruit protein partners for its functional roles. The importance to dissect the role of copper-PrPC interactions in health and disease is also underscored.

Gut microbiota in a population highly affected by obesity and type 2 diabetes and susceptibility to COVID-19.

Coronavirus disease 2019 (COVID-19) is a disease produced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and it is currently causing a catastrophic pandemic affecting humans worldwide. This disease has been lethal for approximately 3.12 million people around the world since January 2020. Globally, among the most affected countries, Mexico ranks third in deaths after the United States of America and Brazil. Although the high number of deceased people might also be explained by social aspects and lifestyle customs in Mexico, there is a relationship between this high proportion of deaths and comorbidities such as high blood pressure (HBP), type 2 diabetes, obesity, and metabolic syndrome. The official epidemiological figures reported by the Mexican government have indicated that 18.4% of the population suffers from HBP, close to 10.3% of adults suffer from type 2 diabetes, and approximately 36.1% of the population suffers from obesity. Disbalances in the gut microbiota (GM) have been associated with these diseases and with COVID-19 severity, presumably due to inflammatory dysfunction. Recent data about the association between GM dysbiosis and metabolic diseases could suggest that the high levels of susceptibility to SARS-CoV-2 infection and COVID-19 morbidity in the Mexican population are primarily due to the prevalence of type 2 diabetes, obesity, and metabolic syndrome.

Amyloid ß Perturbs Cu(II) Binding to the Prion Protein in a Site-Specific Manner: Insights into Its Potential Neurotoxic Mechanisms.

Amyloid ß (Aß) is a Cu-binding peptide that plays a key role in the pathology of Alzheimer's disease. A recent report demonstrated that Aß disrupts the Cu-dependent interaction between cellular prion protein (PrPC) and N-methyl-d-aspartate receptor (NMDAR), inducing overactivation of NMDAR and neurotoxicity. In this context, it has been proposed that Aß competes for Cu with PrPC; however, there is no spectroscopic evidence to support this hypothesis. Prion protein (PrP) can bind up to six Cu(II) ions: from one to four at the octarepeat (OR) region, producing low- and high-occupancy modes, and two at the His96 and His111 sites. Additionally, PrPC is cleaved by α-secretases at Lys110/His111, yielding a new Cu(II)-binding site at the α-cleaved His111. In this study, the competition for Cu(II) between Aß(1-16) and peptide models for each Cu-binding site of PrP was evaluated using circular dichroism and electron paramagnetic resonance. Our results show that the impact of Aß(1-16) on Cu(II) coordination to PrP is highly site-specific: Aß(1-16) cannot effectively compete with the low-occupancy mode at the OR region, whereas it partially removes the metal ion from the high-occupancy modes and forms a ternary OR-Cu(II)-Aß(1-16) complex. In contrast, Aß(1-16) removes all Cu(II) ions from the His96 and His111 sites without formation of ternary species. Finally, at the α-cleaved His111 site, Aß(1-16) yields at least two different ternary complexes depending on the ratio of PrP/Cu(II)/Aß. Altogether, our spectroscopic results indicate that only the low-occupancy mode at the OR region resists the effect of Aß, while Cu(II) coordination to the high-occupancy modes and all other tested sites of PrP is perturbed, by either removal of the metal ion or formation of ternary complexes. These results provide important insights into the intricate effect of Aß on Cu(II) binding to PrP and the potential neurotoxic mechanisms through which Aß might affect Cu-dependent functions of PrPC, such as NMDAR modulation.

Gut Microbiota Alterations and Cognitive Impairment Are Sexually Dissociated in a Transgenic Mice Model of Alzheimer's Disease.

BACKGROUND: Normal aging is accompanied by cognitive deficiencies, affecting women and men equally. Aging is the main risk factor for Alzheimer's disease (AD), with women having a higher risk. The higher prevalence of AD in women is associated with the abrupt hormonal decline seen after menopause. However, other factors may be involved in this sex-related cognitive decline. Alterations in gut microbiota (GM) and its bioproducts have been reported in AD subjects and transgenic (Tg) mice, having a direct impact on brain amyloid-ß pathology in male (M), but not in female (F) mice. OBJECTIVE: The aim of this work was to determine GM composition and cognitive dysfunction in M and F wildtype (WT) and Tg mice, in a sex/genotype segregation design. METHODS: Anxiety, short term working-memory, spatial learning, and long-term spatial memory were evaluated in 6-month-old WT and Tg male mice. Fecal short chain fatty acids were determined by chromatography, and DNA sequencing and bioinformatic analyses were used to determine GM differences. RESULTS: We observed sex-dependent differences in cognitive skills in WT mice, favoring F mice. However, the cognitive advantage of females was lost in Tg mice. GM composition showed few sex-related differences in WT mice. Contrary, Tg-M mice presented a more severe dysbiosis than Tg-F mice. A decreased abundance of Ruminococcaceae was associated with cognitive deficits in Tg-F mice, while butyrate levels were positively associated with better working- and object recognition-memory in WT-F mice. CONCLUSION: This report describes a sex-dependent association between GM alterations and cognitive impairment in a mice model of AD.

Bioactive Foods Decrease Liver and Brain Alterations Induced by a High-Fat-Sucrose Diet through Restoration of Gut Microbiota and Antioxidant Enzymes.

Obesity is associated with cognitive deficit and liver alterations; however, it remains unclear whether a combination of functional foods could reverse cognitive damage and to what extent it would be associated with changes in gut microbiota and liver. With this aim, male Wistar rats were fed a high-fat-5%sucrose diet (HFS) for 4 mo. And were then fed for 1 mo. with bioactive foods. At the end of this period, liver, serum, feces, intestine, and brain samples were taken. Body composition, energy expenditure, LPS, hormones, intraperitoneal glucose tolerance test, behavioral tests, and gut microbiota were evaluated. We showed that male rats fed high-fat-sucrose diet developed gut microbiota dysbiosis, increased in body fat, decreased antioxidant activity, decreased brain neuropeptide Y, increased the number of astrocytes and activated microglia, along with reduced spine density associated with deficits in working memory. Ingestion of a combination of nopal, soy protein, curcumin, and chia seed oil (bioactive foods) for three months was associated with an increase in a cluster of bacteria with anti-inflammatory capacity, a decrease in serum LPS levels and an increase in serum eicosapentaenoic acid (EPA) with neuroprotective properties. In the liver, ingestion of bioactive food significantly increased antioxidant enzymes, decreased lipogenesis, reduced inflammation mediated by the TLR4-TNFα pathway along with a decrease in body fat, glucose intolerance, and metabolic inflexibility. Finally, neuroinflammation in the brain was reduced and working memory improved. Our study demonstrates that consumption of bioactive foods was associated with reduced liver, brain, and gut microbiota alterations in obese rats.

Increased oxidative stress, hyperphosphorylation of tau, and dystrophic microglia in the hippocampus of aged Tupaia belangeri.

Aging is a major risk factor for the development of neurodegenerative diseases. Alzheimer's disease and other neurodegenerative diseases are characterized by abnormal and prominent protein aggregation in the brain, partially due to deficiency in protein clearance. It has been proposed that alterations in microglia phagocytosis and debris clearance hasten the onset of neurodegeneration. Dystrophic microglia are abundant in aged humans, and it has been associated with the onset of disease. Furthermore, alterations in microglia containing ferritin are associated with neurodegenerative conditions. To further understand the process of microglia dysfunction during the aging process, we used hippocampal sections from Tupaia belangeri (tree shrews). Adult (mean age 3.8 years), old (mean age 6 years), and aged (mean age 7.5 years) tree shrews were used for histochemical and immunostaining techniques to determine ferritin and Iba1 positive microglia, iron tissue content, tau hyperphosphorylation and oxidized-RNA in dentate gyrus, subiculum, and CA1-CA3 hippocampal regions. Our results indicated that aged tree shrews presented an increased number of activated microglia containing ferritin, but microglia labeled with Iba1 with a dystrophic phenotype was more abundant in aged individuals. With aging, oxidative damage to RNA (8OHG) increased significantly in all hippocampal regions, while tau hyperphosphorylation (AT100) was enhanced in DG, CA3, and SUB in aged animals. Phagocytic inclusions of 8OHG- and AT100-damaged cells were observed in activated M2 microglia in old and aged animals. These data indicate that aged tree shrew may be a suitable model for translational research to study brain and microglia alterations during the aging process.

A Low Cost Antibody Signal Enhancer Improves Immunolabeling in Cell Culture, Primate Brain and Human Cancer Biopsy.

The use of antibodies to identify neuronal receptors, neurotransmitters, cytoskeletal elements or pathologic protein aggregates, ion channels, adhesion molecules or other cell-type specific markers, is common practice in neuroscience. Antibody detection systems are often based on confocal, epifluorescence or brightfield microscopy. Three types of technical issues can interfere with immunolabeling: low abundance of the target protein, low specific affinity of the antibody and/or signal background sometimes related to tissue fixation. Here, giving tribute to Professor Miledi's mentorship, we propose the application of an antibody signal enhancer (ASE) solution based on glycine, hydrogen peroxide and a detergent mix as a simple, low cost, protocol variation that significantly and specifically improves the signal to noise ratio during immunostaining experiments. We describe three new settings in which ASE improves the detection of a variety of antibodies applied on long-time stored non-human primate brain sections, cell culture monolayers and on squamous carcinomas retrieved from cervical cancer patients. The significant improvement of ASE over optimized immunohistochemical protocols used in clinical practice (i.e. cancer detection) combined with its simplicity and low cost makes it an attractive method for biomedical applications.

Re-thinking the Etiological Framework of Neurodegeneration.

Neurodegenerative diseases are among the leading causes of disability and death worldwide. The disease-related socioeconomic burden is expected to increase with the steadily increasing life expectancy. In spite of decades of clinical and basic research, most strategies designed to manage degenerative brain diseases are palliative. This is not surprising as neurodegeneration progresses "silently" for decades before symptoms are noticed. Importantly, conceptual models with heuristic value used to study neurodegeneration have been constructed retrospectively, based on signs and symptoms already present in affected patients; a circumstance that may confound causes and consequences. Hence, innovative, paradigm-shifting views of the etiology of these diseases are necessary to enable their timely prevention and treatment. Here, we outline four alternative views, not mutually exclusive, on different etiological paths toward neurodegeneration. First, we propose neurodegeneration as being a secondary outcome of a primary cardiovascular cause with vascular pathology disrupting the vital homeostatic interactions between the vasculature and the brain, resulting in cognitive impairment, dementia, and cerebrovascular events such as stroke. Second, we suggest that the persistence of senescent cells in neuronal circuits may favor, together with systemic metabolic diseases, neurodegeneration to occur. Third, we argue that neurodegeneration may start in response to altered body and brain trophic interactions established via the hardwire that connects peripheral targets with central neuronal structures or by means of extracellular vesicle (EV)-mediated communication. Lastly, we elaborate on how lifespan body dysbiosis may be linked to the origin of neurodegeneration. We highlight the existence of bacterial products that modulate the gut-brain axis causing neuroinflammation and neuronal dysfunction. As a concluding section, we end by recommending research avenues to investigate these etiological paths in the future. We think that this requires an integrated, interdisciplinary conceptual research approach based on the investigation of the multimodal aspects of physiology and pathophysiology. It involves utilizing proper conceptual models, experimental animal units, and identifying currently unused opportunities derived from human data. Overall, the proposed etiological paths and experimental recommendations will be important guidelines for future cross-discipline research to overcome the translational roadblock and to develop causative treatments for neurodegenerative diseases.

Loss of ferritin-positive microglia relates to increased iron, RNA oxidation, and dystrophic microglia in the brains of aged male marmosets.

Microglia are cells that protect brain tissue from invading agents and toxic substances, first by releasing pro-inflammatory cytokines, and thereafter by clearing tissue by phagocytosis. Microglia express ferritin, a protein with ferroxidase activity capable of storing iron, a metal that accumulates in brain during aging. Increasing evidence suggests that ferritin plays an important role in inflammation. However, it is not known if ferritin/iron content can be related to the activation state of microglia. To this end, we aimed to delineate the role of ferritin in microglia activation in a non-human primate model. We analyzed brains of male marmosets and observed an increased density of ferritin+ microglia with an activated phenotype in hippocampus and cortex of old marmosets (mean age 11.25 ± 0.70 years) compared to younger subjects. This was accompanied by an increased number of dystrophic microglia in old marmosets. However, in aged subjects (mean age 16.83 ± 2.59 years) the number of ferritin+ microglia was decreased compared to old ones. Meanwhile, the content of iron in brain tissue and cells with oxidized RNA increased during aging in all hippocampal and cortical regions analyzed. Abundant amoeboid microglia were commonly observed surrounding neurons with oxidized RNA. Notably, amoeboid microglia were arginase1+ and IL-10+, indicative of a M2 phenotype. Some of those M2 cells also presented RNA oxidation and a dystrophic phenotype. Therefore, our data suggest that ferritin confers protection to microglia in adult and old marmosets, while in aged subjects the decline in ferritin and the increased amount of iron in brain tissue may be related to the increased number of cells with oxidized RNA, perhaps precluding the onset of neurodegeneration.

Bioactive Food Abates Metabolic and Synaptic Alterations by Modulation of Gut Microbiota in a Mouse Model of Alzheimer's Disease.

Recent investigations have demonstrated an important role of gut microbiota (GM) in the pathogenesis of Alzheimer's disease (AD). GM modulates a host's health and disease by production of several substances, including lipopolysaccharides (LPS) and short-chain fatty acids (SCFAs), among others. Diet can modify the composition and diversity of GM, and ingestion of a healthy diet has been suggested to lower the risk to develop AD. We have previously shown that bioactive food (BF) ingestion can abate neuroinflammation and oxidative stress and improve cognition in obese rats, effects associated with GM composition. Therefore, BF can impact the gut-brain axis and improved behavior. In this study, we aim to explore if inclusion of BF in the diet may impact central pathological markers of AD by modulation of the GM. Triple transgenic 3xTg-AD (TG) female mice were fed a combination of dried nopal, soy, chia oil, and turmeric for 7 months. We found that BF ingestion improved cognition and reduced Aß aggregates and tau hyperphosphorylation. In addition, BF decreased MDA levels, astrocyte and microglial activation, PSD-95, synaptophysin, GluR1 and ARC protein levels in TG mice. Furthermore, TG mice fed BF showed increased levels of pGSK-3ß. GM analysis revealed that pro-inflammatory bacteria were more abundant in TG mice compared to wild-type, while BF ingestion was able to restore the GM's composition, LPS, and propionate levels to control values. Therefore, the neuroprotective effects of BF may be mediated, in part, by modulation of GM and the release of neurotoxic substances that alter brain function.

Long-Term Genistein Consumption Modifies Gut Microbiota, Improving Glucose Metabolism, Metabolic Endotoxemia, and Cognitive Function in Mice Fed a High-Fat Diet.

SCOPE: The aim of this study is to assess whether the long-term addition of genistein to a high-fat diet can ameliorate the metabolic and the cognitive alterations and whether the changes can be associated with modifications to the gut microbiota. METHODS AND RESULTS: C57/BL6 mice were fed either a control (C) diet, a high-fat (HF) diet, or a high-fat diet containing genistein (HFG) for 6 months. During the study, indirect calorimetry, IP glucose tolerance tests, and behavioral analyses were performed. At the end of the study, plasma, liver, brain, and fecal samples were collected. The results showed that mice fed the HFG diet gained less weight, had lower serum triglycerides, and an improvement in glucose tolerance than those fed an HF diet. Mice fed the HFG diet also modified the gut microbiota that was associated with lower circulating levels of lipopolysaccharide (LPS) and reduced expression of pro-inflammatory cytokines in the liver compared to those fed HF diet. The reduction in LPS by the consumption of genistein was accompanied by an improvement of the cognitive function. CONCLUSIONS: Genistein is able to regulate the gut microbiota, reducing metabolic endotoxemia and decreasing the neuroinflammatory response despite the consumption of a HF diet.

Nopal (Opuntia ficus indica) protects from metabolic endotoxemia by modifying gut microbiota in obese rats fed high fat/sucrose diet.

Current efforts are directed to reducing the gut dysbiosis and inflammation produced by obesity. The purpose of this study was to investigate whether consuming nopal, a vegetable rich in dietary fibre, vitamin C, and polyphenols can reduce the metabolic consequences of obesity by modifying the gut microbiota and preventing metabolic endotoxemia in rats fed a high fat and sucrose diet. With this aim, rats were fed a high fat diet with 5% sucrose in the drinking water (HFS) for 7 months and then were fed for 1 month with HFS + 5% nopal (HFS + N). The composition of gut microbiota was assessed by sequencing the 16S rRNA gene. Nopal modified gut microbiota and increased intestinal occludin-1 in the HFS + N group. This was associated with a decrease in metabolic endotoxemia, glucose insulinotropic peptide, glucose intolerance, lipogenesis, and metabolic inflexibility. These changes were accompanied by reduced hepatic steatosis and oxidative stress in adipose tissue and brain, and improved cognitive function, associated with an increase in B. fragilis. This study supports the use of nopal as a functional food and prebiotic for its ability to modify gut microbiota and to reduce metabolic endotoxemia and other obesity-related biochemical abnormalities.