Maternal Sweeteners Intake Modulates Gut Microbiota and Exacerbates Learning and Memory Processes in Adult Male Offspring

Background: There is increasing evidence that gut microbiota in offspring is derived in part from maternal environment such as diet. Thus, sweeteners intake including caloric or non-caloric during perinatal period can induce gut dysbiosis and program the offspring to develop cognitive problems later in life.Objective: To determine the effect of maternal high-sweeteners intake during gestation and lactation on gut microbiota shifts in adult male offspring rats and the impact on cognitive dysfunction.Methods: Thirty-four male pups from dams fed standard diet (Control-C, n = 10), high-sucrose diet (HS-C, n = 11), high-honey diet (Ho-C, n = 8), and high-stevia diet (HSt-C, n = 5) were fed standard diet after weaning, and body weight and food intake were recorded once a week for 26 weeks. Learning and memory tests were performed at week 23 of life using the Barnes maze. Fecal samples from the breastfeeding and adulthood periods were collected and analyzed by sequencing the 16S rRNA V3-V4 region of gut microbiota.Results: Maternal high-sucrose and stevia diets programmed the male offspring, and changes in microbial diversity by Shannon index were observed after weaning (p < 0.01). Furthermore, maternal high-stevia diet programming lasted into adulthood. The increase of Firmicutes abundance and the decrease in phylum Bacteroidetes were significant in HS-C and HSt-C groups. This led to an increase in the Firmicutes/Bacteroidetes index, although only in HS-C group was statistically significant (p < 0.05). Of note, the downstream gram-negative Bacteroidales and the upregulation of the gram-positive Clostridiales abundance contribute to cognitive dysfunction.Conclusion: These results suggest that dams fed a high-sucrose and stevia diets during gestation and lactation favor a deficient memory performance in adult male offspring rats through shifts gut microbiota diversity and relative abundance at several taxa.

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Effects of Psychotropics on the Microbiome in Patients With Depression and Anxiety: Considerations in a Naturalistic Clinical Setting

The International Journal of Neuropsychopharmacology ◽

10.1093/ijnp/pyaa070 ◽

2020 ◽

Author(s):

Yoshihiro Tomizawa ◽

Shunya Kurokawa ◽

Daiki Ishii ◽

Katsuma Miyaho ◽

Chiharu Ishii ◽

...

Keyword(s):

Gut Microbiota ◽

Microbial Diversity ◽

Depressive Disorders ◽

Alpha Diversity ◽

16S Rrna Gene Sequencing ◽

Shannon Index ◽

Rrna Gene ◽

Depression And Anxiety ◽

The Impact ◽

Whole Tree

Abstract Background The antibacterial effects of psychotropics may be part of their pharmacological effects when treating depression. However, limited studies have focused on gut microbiota in relation to prescribed medication. Method We longitudinally investigated the relationship between patients’ prescribed medications and intestinal bacterial diversity in a naturalistic treatment course for patients with major depressive disorders and anxiety disorders. Patients were recruited and their stool was collected at 3 time points during their usual psychiatric treatments. Gut microbiota were analyzed using 16S rRNA gene sequencing. We examined the impact of psychotropics (i.e., antidepressants, anxiolytics, antipsychotics) on their gut microbial diversity and functions. Results We collected 246 stool samples from 40 patients. Despite no differences in microbial diversity between medication groups at the baseline, over the course of treatment, phylogenic diversity whole-tree diversity decreased in patients on antipsychotics compared with patients without (P = .027), and beta diversity followed this trend. Based on a fixed-effect model, antipsychotics predicted microbial diversity; the higher doses correlated with less diversity based on the Shannon index and phylogenic diversity whole tree (estimate = −0.00254, SE = 0.000595, P < .0001; estimate = −0.02644, SE = 0.00833, P = .002, respectively). Conclusion Antipsychotics may play a role in decreasing the alpha diversity of the gut microbiome among patients with depression and anxiety, and our results indicate a relationship with medication dosage. Future studies are warranted and should consider patients’ types and doses of antipsychotics in order to further elucidate the mechanisms of gut-brain interactions in psychiatric disorders.

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Maternal Adenine-Induced Chronic Kidney Disease Programs Hypertension in Adult Male Rat Offspring: Implications of Nitric Oxide and Gut Microbiome Derived Metabolites

International Journal of Molecular Sciences ◽

10.3390/ijms21197237 ◽

2020 ◽

Vol 21 (19) ◽

pp. 7237 ◽

Cited By ~ 2

Author(s):

Chien-Ning Hsu ◽

Hung-Wei Yang ◽

Chih-Yao Hou ◽

Guo-Ping Chang-Chien ◽

Sufan Lin ◽

...

Keyword(s):

Nitric Oxide ◽

Chronic Kidney Disease ◽

Kidney Disease ◽

Gut Microbiota ◽

Adult Male ◽

Male Offspring ◽

Uremic Toxin ◽

Microbiota Composition ◽

Adverse Pregnancy ◽

Gut Microbiota Composition

Maternal chronic kidney disease (CKD) during pregnancy causes adverse fetal programming. Nitric oxide (NO) deficiency, gut microbiota dysbiosis, and dysregulated renin-angiotensin system (RAS) during pregnancy are linked to the development of hypertension in adult offspring. We examined whether maternal adenine-induced CKD can program hypertension and kidney disease in adult male offspring. We also aimed to identify potential mechanisms, including alterations of gut microbiota composition, increased trimethylamine-N-oxide (TMAO), reduced NO bioavailability, and dysregulation of the RAS. To construct a maternal CKD model, female Sprague-Dawley rats received regular chow (control group) or chow supplemented with 0.5% adenine (CKD group) for 3 weeks before pregnancy. Mother rats were sacrificed on gestational day 21 to analyze placentas and fetuses. Male offspring (n = 8/group) were sacrificed at 12 weeks of age. Adenine-fed rats developed renal dysfunction, glomerular and tubulointerstitial damage, hypertension, placental abnormalities, and reduced fetal weights. Additionally, maternal adenine-induced CKD caused hypertension and renal hypertrophy in adult male offspring. These adverse pregnancy and offspring outcomes are associated with alterations of gut microbiota composition, increased uremic toxin asymmetric and symmetric dimethylarginine (ADMA and SDMA), increased microbiota-derived uremic toxin TMAO, reduced microbiota-derived metabolite acetate and butyrate levels, and dysregulation of the intrarenal RAS. Our results indicated that adenine-induced maternal CKD could be an appropriate model for studying uremia-related adverse pregnancy and offspring outcomes. Targeting NO pathway, microbiota metabolite TMAO, and the RAS might be potential therapeutic strategies to improve maternal CKD-induced adverse pregnancy and offspring outcomes.

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Dysfunction of EAAT3 Enhances LPS-induced Postoperative Cognitive Dysfunction

10.21203/rs.3.rs-169684/v1 ◽

2021 ◽

Author(s):

Xiaoyan Wang ◽

Yulong Ma ◽

Aisheng Hou ◽

Yuxiang Song ◽

Xin Sui ◽

...

Keyword(s):

Membrane Protein ◽

Protein Expression ◽

Learning And Memory ◽

Cognitive Dysfunction ◽

Adult Male ◽

Excitatory Amino Acid ◽

Postoperative Cognitive Dysfunction ◽

Male Mice ◽

Membrane Protein Expression

Abstract Background: Studies have shown that excitatory amino acid transporter 3 (EAAT3) function inhibition is related to several neurodegenerative diseases. Our previous studies also found that the EAAT3 function is intimately linked to learning and memory. In this study, we examined the role of EAAT3 in postoperative cognitive dysfunction (POCD) and explored the potential benefit of riluzole against POCD. Methods: We measured EAAT3 protein expression in hippocampus of male mice at different ages. Next, we established a recombinant adeno-associated viral (rAAV)-mediated shRNA to knockdown EAAT3 expression in the hippocampus of adult male mice. And then the mice received 2μg of lipopolysaccharide (LPS) intracerebroventricular microinjection to construct the POCD model. In addition, we intraperitoneally injected 4mg/kg of riluzole 2 days before LPS microinjection for consecutive 3 days in elderly male mice. Cognitive function was assessed using a Morris water maze 24h after LPS microinjection. Animal behavioral tests, as well as pathological and biochemical assays, were performed to clarify the role of EAAT3 function in POCD and evaluate the effect of activation of EAAT3 function by riluzole. Results: We found that the expression of EAAT3 was significantly decreased in old mice and EAAT3 knockdown in hippocampus aggravated LPS-induced learning and memory deficits in adult male mice. LPS significantly inhibited hippocampal EAAT3 membrane protein expression and GluA1 protein phosphorylation level in adult male mice. Moreover, riluzole pretreatment significantly increased hippocampal EAAT3 membrane protein expression and ameliorated LPS-induced cognitive impairment in old male mice. Conclusions: Our results demonstrated that the dysfunction of EAAT3 is an important risk factor for POCD susceptibility and riluzole may be a promising strategy for prevention and treating of POCD in the elderly people.

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Synbiotic Supplementation Modulates Gut Microbiota, Regulates Beta-Catenin Expression And Prevents Weight Gain in ob/ob Mice

10.21203/rs.3.rs-655169/v2 ◽

2021 ◽

Author(s):

Sebastião Mauro Bezerra Duarte ◽

José Tadeu Stefano ◽

Lucas A. M. Franco ◽

Roberta C. Martins ◽

Bruna D. G. C. Moraes ◽

...

Keyword(s):

Gene Expression ◽

Weight Gain ◽

Gut Microbiota ◽

Body Weight Gain ◽

Standard Diet ◽

Beta Catenin ◽

Reduced Body ◽

Synbiotic Supplementation ◽

And Control ◽

The Impact

Abstract Background: The aim of this study was to examine the impact of synbiotic supplementation in obesity and microbiota in ob/ob mice. 20 animals were divided into four groups: Obese Treated (OT), Control (OC), Lean Treated (LT) and Control (LC). All animals received standard diet for 8 weeks. Treated groups received a synbiotic in water while nontreated groups received water. After 8 weeks, all animals were sacrificed and gut tissue mRNA isolation and stool samples by microbiota analysis were collected. Beta-catenin, occludin, cadherin and zonulin were analyzed in gut tissue by RT-qPCR. Results: The synbiotic supplementation reduced body weight gain in OT comparing with OC (p=0.0398), increase of Enterobacteriaceae (p=0.005) and decrease of Cyanobacteria (p=0.047), Clostridiaceae (p=0.026), Turicibacterales (p=0.005) and Coprococcus (p=0.047). A significant reduction of Sutterella bacteria (p=0.009) and Turicibacter (p=0.005) was observed in LT compared to LC. Alpha and beta diversities were differ between all treated groups. Beta-catenin gene expression was significantly decreased in the gut tissue of OT (p≤0.0001) when compared to other groups. No changes were observed in occludin, cadherin and zonulin gene expression in the gut tissue. Conclusion: The synbiotics supplementation prevents excessive weight gain, modulates the gut microbiota, and reduces beta-catenin expression in ob/ob mice.

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The Effect of Host, Habitat and Fasting Time on the Gut Microbiota of Amphibian

10.21203/rs.3.rs-162992/v1 ◽

2021 ◽

Author(s):

Qing Tong ◽

Li-yong Cui ◽

Zong-fu Hu ◽

Xiao-peng Du ◽

Hong-bin Wang

Keyword(s):

Environmental Factors ◽

Gut Microbiota ◽

Environmental Changes ◽

Early Stage ◽

Information Criterion ◽

Shannon Index ◽

Lifestyle Changes ◽

Fasting Time ◽

The Impact ◽

Late Stages

Abstract Wild animals entering captivity experience radical lifestyle changes resulting in microbiota alterations, in large part due to differences in diet. However, little is known about how external environmental factors influences the gut microbiota and the interaction of the environment-host-microbe interactions in host fasting. The gut microbiota in the early stage (amA and dyA groups) and late stage of hibernation in Rana amurensis and R. dybowskii of entering captivity (amL and dyL groups) and wild environments (amS and dyS groups) was determined, and the effects of host, environmental factors and fasting time on the gut microbiota were investigated via high-throughput Illumina sequencing. The Shannon index differed significantly between the amL and dyL groups and between the amA and amS groups. The PD index differed significantly between the dyL and dyS groups. Eight core OTUs were widely distributed between species, habitats and fasting times and were dominant in abundance. Captive and wild environments, host species, and fasting time significantly affected the composition and structure of the gut microbiota. Akaike information criterion (AIC)-based model results suggested that the environment and host were the variables that needed to be included in redundancy analysis (RDA) to explain the variance in taxa. The pairwise distances between the early and late stages of hibernation of were greater in R. amurensis and R. dybowskii entering captivity than in wild. The average of OTUs shared by early and late stages of hibernation of captive frogs was significantly lower than the average of wild frogs. These results can reveal the impact of environmental changes on the gut microbiota, thereby revealing the important interactions between environment-host-microbes, and helping to protect vertebrate hosts.

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High Salt Elicits Brain Inflammation and Cognitive Dysfunction, Accompanied by Alternations in the Gut Microbiota and Decreased SCFA Production

Journal of Alzheimer s Disease ◽

10.3233/jad-200035 ◽

2020 ◽

Vol 77 (2) ◽

pp. 629-640

Author(s):

Li Hu ◽

Shaoping Zhu ◽

Xiaoping Peng ◽

Kanglan Li ◽

Wanjuan Peng ◽

...

Keyword(s):

Gut Microbiota ◽

Learning And Memory ◽

Cognitive Dysfunction ◽

Caspase 3 ◽

Bacterial Flora ◽

High Salt ◽

Brain Inflammation ◽

Control Group ◽

Spatial Learning And Memory ◽

The Brain

Background: Excessive salt intake is considered as an important risk factor for cognitive impairment, which might be the consequence of imbalanced intestinal homeostasis. Objective: To investigate the effects of dietary salt on the gut microbiota and cognitive performance and the underlying mechanisms. Methods: Adult female C57BL/6 mice were maintained on either normal chow (control group, CON) or sodium-rich chow containing 8% NaCl (high-salt diet, HSD) for 8 weeks. Spatial learning and memory ability, short-chain fatty acids (SCFAs) concentrations, gut bacterial flora composition, blood-brain barrier permeability, and proinflammatory cytokine levels and apoptosis in the brain were evaluated. Results: The mice fed a HSD for 8 weeks displayed impaired learning and memory abilities. HSD significantly reduced the proportions of Bacteroidetes (S24-7 and Alloprevotella) and Proteobacteria and increased that of Firmicutes (Lachnospiraceae and Ruminococcaceae). SCFA concentrations decreased in the absolute concentrations of acetate, propionate, and butyrate in the fecal samples from the HSD-fed mice. The HSD induced both BBB dysfunction and microglial activation in the mouse brain, and increased the IL-1β, IL-6, and TNF-α expression levels in the cortex. More importantly, the degree of apoptosis was higher in the cortex and hippocampus region of mice fed the HSD, and this effect was accompanied by significantly higher expression of cleaved caspase-3, caspase-3, and caspase-1. Conclusion: The HSD directly causes cognitive dysfunction in mice by eliciting an inflammatory environment and triggering apoptosis in the brain, and these effects are accompanied by gut dysbiosis, particularly reduced SCFA production.

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Effect of electronic cigarette aerosol exposure during gestation and lactation on learning and memory of adult male offspring rats

Physiology & Behavior ◽

10.1016/j.physbeh.2020.112911 ◽

2020 ◽

Vol 221 ◽

pp. 112911

Author(s):

Nour Al-Sawalha ◽

Karem Alzoubi ◽

Omar Khabour ◽

Nareg Karaoghlanian ◽

Zahi Ismail ◽

...

Keyword(s):

Learning And Memory ◽

Adult Male ◽

Electronic Cigarette ◽

Male Offspring ◽

Aerosol Exposure

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Dysfunction of EAAT3 enhances LPS-induced Postoperative Cognitive Dysfunction

10.21203/rs.3.rs-141076/v3 ◽

2021 ◽

Author(s):

Xiaoyan Wang ◽

Yulong Ma ◽

Aisheng Hou ◽

Yuxiang Song ◽

Xin Sui ◽

...

Keyword(s):

Membrane Protein ◽

Protein Expression ◽

Learning And Memory ◽

Cognitive Dysfunction ◽

Adult Male ◽

Excitatory Amino Acid ◽

Postoperative Cognitive Dysfunction ◽

Male Mice ◽

Membrane Protein Expression

Abstract Background Studies have shown that excitatory amino acid transporter 3 (EAAT3) function inhibition is related to several neurodegenerative diseases. Our previous studies also found that the EAAT3 function is intimately linked to learning and memory. In this study, we examined the role of EAAT3 in postoperative cognitive dysfunction (POCD) and explored the potential benefit of riluzole against POCD. Methods We measured EAAT3 protein expression in hippocampus of male mice at different ages. Next, we established a recombinant adeno-associated viral (rAAV)-mediated shRNA to knockdown EAAT3 expression in the hippocampus of adult male mice. And then the mice received 2µg of lipopolysaccharide (LPS) intracerebroventricular microinjection to construct the POCD model. In addition, we intraperitoneally injected 4mg/kg of riluzole 2 days before LPS microinjection for consecutive 3 days in elderly male mice. Cognitive function was assessed using a Morris water maze 24h after LPS microinjection. Animal behavioral tests, as well as pathological and biochemical assays, were performed to clarify the role of EAAT3 function in POCD and evaluate the effect of activation of EAAT3 function by riluzole. Results We found that the expression of EAAT3 was significantly decreased in old mice and EAAT3 knockdown in hippocampus aggravated LPS-induced learning and memory deficits in adult male mice. LPS significantly inhibited hippocampal EAAT3 membrane protein expression and GluA1 protein phosphorylation level in adult male mice. Moreover, riluzole pretreatment significantly increased hippocampal EAAT3 membrane protein expression and ameliorated LPS-induced cognitive impairment in old male mice. Conclusions Our results demonstrated that the dysfunction of EAAT3 is an important risk factor for POCD susceptibility and riluzole may be a promising strategy for prevention and treating of POCD in the elderly people.

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Synbiotic Supplementation Modulates Gut Microbiota, Regulates Beta-catenin Expression and Prevents Weight Gain in Ob/ob Mice

10.21203/rs.3.rs-655169/v1 ◽

2021 ◽

Author(s):

Sebastião Mauro Bezerra Duarte ◽

José Tadeu Stefano ◽

Lucas A. M. Franco ◽

Roberta C. Martins ◽

Bruna D. G. C. Moraes ◽

...

Keyword(s):

Gene Expression ◽

Weight Gain ◽

Gut Microbiota ◽

Body Weight Gain ◽

Standard Diet ◽

Beta Catenin ◽

Stool Samples ◽

Synbiotic Supplementation ◽

And Control ◽

The Impact

Abstract Background: Obesity is one of the main health problems in the world today and dysbiosis seem to be one of the factors involved. The aim of this study was to examine the impact of synbiotic supplementation in obesity and microbiota in ob/ob mice. 20 animals were divided into four groups: Obese Treated (OT) and Control (OC), Lean Treated (LT) and Control (LC). All animals received standard diet for 8 weeks. Treated groups received a synbiotic in water while nontreated groups received water. After 8 weeks, all animals were sacrificed and gut tissue mRNA isolation and stool samples by microbiota analysis were collected. Beta-catenin, occludin, cadherin and zonulin were analyzed in gut tissue by RT-qPCR. Microbiome DNA was extracted from stool samples and sequenced using the Ion PGM Torrent platform. Results: The synbiotic supplementation reduced body weight gain in OT group comparing with OC (p=0.0398), increase of Enterobacteriaceae (p=0.005) and decrease of Cyanobacteria (p=0.047), Clostridiaceae (p=0.026), Turicibacterales (p=0.005) and Coprococcus (p=0.047). In the other hand, a significant reduction of Sutterella bacteria (p=0.009) and Turicibacter (p=0.005) was observed in LT group compared to LC. Alpha and beta diversities were differ between all treated groups. Beta-catenin gene expression was significantly decreased in the gut tissue of OT group (p≤0.0001) when compared to other groups. No changes were observed in occludin, cadherin and zonulin gene expression in the gut tissue. Conclusion: The synbiotics supplementation prevents excessive weight gain, modulates the gut microbiota, and reduces beta-catenin expression in ob/ob mice.

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Dietary magnesium deficiency affects gut microbiota and anxiety-like behaviour in C57BL/6N mice

Acta Neuropsychiatrica ◽

10.1017/neu.2015.10 ◽

2015 ◽

Vol 27 (5) ◽

pp. 307-311 ◽

Cited By ~ 17

Author(s):

Bettina Pyndt Jørgensen ◽

Gudrun Winther ◽

Pernille Kihl ◽

Dennis S. Nielsen ◽

Gregers Wegener ◽

...

Keyword(s):

Gut Microbiota ◽

Magnesium Deficiency ◽

Standard Diet ◽

Microbiota Composition ◽

Deficient Diet ◽

Anxiety Test ◽

Dietary Magnesium ◽

Gradient Gel Electrophoresis ◽

The Impact ◽

Gut Microbiota Composition

ObjectiveMagnesium deficiency has been associated with anxiety in humans, and rodent studies have demonstrated the gut microbiota to impact behaviour.MethodsWe investigated the impact of 6 weeks of dietary magnesium deficiency on gut microbiota composition and anxiety-like behaviour and whether there was a link between the two. A total of 20 C57BL/6 mice, fed either a standard diet or a magnesium-deficient diet for 6 weeks, were tested using the light-dark box anxiety test. Gut microbiota composition was analysed by denaturation gradient gel electrophoresis.ResultsWe demonstrated that the gut microbiota composition correlated significantly with the behaviour of dietary unchallenged mice. A magnesium-deficient diet altered the gut microbiota, and was associated with altered anxiety-like behaviour, measured by decreased latency to enter the light box.ConclusionMagnesium deficiency altered behavior. The duration of magnesium deficiency is suggested to influence behaviour in the evaluated test.

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