scholarly journals CD36 deficiency affects depressive-like behaviors possibly by modifying gut microbiota and the inflammasome pathway in mice

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Shunjie Bai ◽  
Wei Wang ◽  
Ting Wang ◽  
Juan Li ◽  
Shuxiao Zhang ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Signaling Pathway ◽  
Nlrp3 Inflammasome ◽  
Depressive Disorders ◽  
Diversity Index ◽  
Scavenger Receptor ◽  
Alpha Diversity ◽  
Rrna Gene ◽  
Cd36 Deficiency ◽  
Class B

AbstractBoth inflammatory processes and gut microbiota have been implicated in the pathophysiology of depressive disorders. The class B scavenger receptor CD36 is involved in the cytotoxicity associated with inflammation. However, its role in depression has not yet been examined. In this study, we investigated whether CD36 affects depression by modulating the microbiota-gut-inflammasome-brain axis. We used CD36−/− (knockout) mice subjected to chronic social defeat stress, and measured the expression of CD36 in these depressed mice and in patients with depression. The hippocampus of CD36−/− mice was used to investigate changes in the NLRP3 inflammasome signaling pathway. The 16S rRNA gene sequence-based approach was used to compare the cecal microbial communities in CD36−/− and WT mice. The CD36 deficiency in CD36−/− mice alleviated chronic stress-induced depression-like behaviors. CD36 was upregulated in depressed mice as well as in depressed patients. Furthermore, the NLRP3 inflammasome signaling pathway was downregulated in the hippocampus of CD36−/− mice. The Simpson Diversity Index revealed increased cecal bacterial alpha-diversity in the CD36−/− mice. Among genera, Bacteroides, Rikenella, and Alloprevotella were significantly more abundant in the CD36−/− mice, whereas Allobaculum was less abundant, consistent with the attenuated inflammation in the hippocampus of CD36−/− mice. Our findings suggest that CD36 deficiency changes the gut microbiota composition, which in turn may impact depressive-like behaviors by affecting the inflammasome pathway.

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

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.

scholarly journals Role of ASM/Cer/TXNIP signaling module in the NLRP3 inflammasome activation

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Jianjun Jiang ◽  
Yining Shi ◽  
Jiyu Cao ◽  
Youjin Lu ◽  
Gengyun Sun ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Nlrp3 Inflammasome ◽  
Mrna Level ◽  
Scavenger Receptor ◽  
Nuclear Factor Κb ◽  
Inflammasome Activation ◽  
Mrna Levels ◽  
Irreversible Inhibitor ◽  
Nlrp3 Inflammasome Activation

Abstract Background This study aimed to explore the effects of ceramide (Cer) on NLRP3 inflammasome activation and their underlying mechanisms. Methods Lipopolysaccharide (LPS)/adenosine triphosphate (ATP)-induced NLRP3 inflammasome activation in J774A.1 cells and THP-1 macrophages was used as an in vitro model of inflammation. Western blotting and real-time PCR (RT-PCR) were used to detect the protein and mRNA levels, respectively. IL-1β and IL-18 levels were measured by ELISA. ASM assay kit and immunofluorescence were used to detect ASM activity and Cer content. Results Imipramine, a well-known inhibitor of ASM, significantly inhibited LPS/ATP-induced activity of ASM and the consequent accumulation of Cer. Additionally, imipramine suppressed the LPS/ATP-induced expression of thioredoxin interacting protein (TXNIP), NLRP3, caspase-1, IL-1β, and IL-18 at the protein and mRNA level. Interestingly verapamil, a TXNIP inhibitor, suppressed LPS/ATP-induced activation of TXNIP/NLRP3 inflammasome but did not affect LPS/ATP-induced ASM activation and Cer formation. TXNIP siRNA and verapamil inhibited C2-Cer-induced upregulation of TXNIP and activation of the NLRP3 inflammasome. In addition, the pretreatment of cells with sulfo-N-succinimidyl oleate (SSO), an irreversible inhibitor of the scavenger receptor CD36, blocked Cer-induced upregulation of nuclear factor-κB (NF-κB) activity, TXNIP expression, and NLRP3 inflammasome activation. Inhibition of NF-κB activation by SN50 prevented Cer-induced upregulation of TXNIP and activation of the NLRP3 inflammasome but did not affect CD36 expression. Conclusion This study demonstrated that the ASM/Cer/TXNIP signaling pathway is involved in NLRP3 inflammasome activation. The results documented that the CD36-dependent NF-κB-TXNIP signaling pathway plays an essential role in the Cer-induced activation of NLRP3 inflammasomes in macrophages.

scholarly journals The Effects of Genetic Relatedness on the Preterm Infant Gut Microbiota

2021 ◽  
Vol 9 (2) ◽  
pp. 278
Author(s):  
Shen Jean Lim ◽  
Miriam Aguilar-Lopez ◽  
Christine Wetzel ◽  
Samia V. O. Dutra ◽  
Vanessa Bray ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Preterm Infant ◽  
Neonatal Intensive Care ◽  
Genetic Relatedness ◽  
Bovine Milk ◽  
Alpha Diversity ◽  
Neonatal Intensive Care Units ◽  
Rrna Gene ◽  
Microbial Composition ◽  
Operational Taxonomic Units

The preterm infant gut microbiota is influenced by environmental, endogenous, maternal, and genetic factors. Although siblings share similar gut microbial composition, it is not known how genetic relatedness affects alpha diversity and specific taxa abundances in preterm infants. We analyzed the 16S rRNA gene content of stool samples, ≤ and >3 weeks postnatal age, and clinical data from preterm multiplets and singletons at two Neonatal Intensive Care Units (NICUs), Tampa General Hospital (TGH; FL, USA) and Carle Hospital (IL, USA). Weeks on bovine milk-based fortifier (BMF) and weight gain velocity were significant predictors of alpha diversity. Alpha diversity between siblings were significantly correlated, particularly at ≤3 weeks postnatal age and in the TGH NICU, after controlling for clinical factors. Siblings shared higher gut microbial composition similarity compared to unrelated individuals. After residualizing against clinical covariates, 30 common operational taxonomic units were correlated between siblings across time points. These belonged to the bacterial classes Actinobacteria, Bacilli, Bacteroidia, Clostridia, Erysipelotrichia, and Negativicutes. Besides the influence of BMF and weight variables on the gut microbial diversity, our study identified gut microbial similarities between siblings that suggest genetic or shared maternal and environmental effects on the preterm infant gut microbiota.

scholarly journals Gut bacterial microbiota in patients with myasthenia gravis: results from the MYBIOM study

2021 ◽  
Vol 14 ◽  
pp. 175628642110356
Author(s):  
Andreas Totzeck ◽  
Elakiya Ramakrishnan ◽  
Melina Schlag ◽  
Benjamin Stolte ◽  
Kathrin Kizina ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Myasthenia Gravis ◽  
Healthy Volunteers ◽  
Alpha Diversity ◽  
Diversity Indices ◽  
Rrna Gene ◽  
Pilot Studies ◽  
Variable Regions ◽  
Alpha And Beta Diversity ◽  
Significant Difference

Background: Myasthenia gravis (MG) is an autoimmune neuromuscular disease, with gut microbiota considered to be a pathogenetic factor. Previous pilot studies have found differences in the gut microbiota of patients with MG and healthy individuals. To determine whether gut microbiota has a pathogenetic role in MG, we compared the gut microbiota of patients with MG with that of patients with non-inflammatory and inflammatory neurological disorders of the peripheral nervous system (primary endpoint) and healthy volunteers (secondary endpoint). Methods: Faecal samples were collected from patients with MG ( n = 41), non-inflammatory neurological disorder (NIND, n = 18), chronic inflammatory demyelinating polyradiculoneuropathy (CIDP, n = 6) and healthy volunteers ( n = 12). DNA was isolated from these samples, and the variable regions of the 16S rRNA gene were sequenced and statistically analysed. Results: No differences were found in alpha- and beta-diversity indices computed between the MG, NIND and CIDP groups, indicating an unaltered bacterial diversity and structure of the microbial community. However, the alpha-diversity indices, namely Shannon, Chao 1 and abundance-based coverage estimators, were significantly reduced between the MG group and healthy volunteers. Deltaproteobacteria and Faecalibacterium were abundant within the faecal microbiota of patients with MG compared with controls with non-inflammatory diseases. Conclusion: Although the overall diversity and structure of the gut microbiota did not differ between the MG, NIND and CIDP groups, the significant difference in the abundance of Deltaproteobacteria and Faecalibacterium supports the possible role of gut microbiota as a contributor to pathogenesis of MG. Further studies are needed to confirm these findings and to develop possible treatment strategies.

scholarly journals Probiotic Supplementation in a Clostridium difficile-Infected Gastrointestinal Model Is Associated with Restoring Metabolic Function of Microbiota

2019 ◽  
Vol 8 (1) ◽  
pp. 60
Author(s):  
Mohd Baasir Gaisawat ◽  
Chad W. MacPherson ◽  
Julien Tremblay ◽  
Amanda Piano ◽  
Michèle M. Iskandar ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Alpha Diversity ◽  
Gastrointestinal Disorder ◽  
Short Chain Fatty Acids ◽  
Rrna Gene ◽  
Metabolic Function ◽  
Microbial Composition ◽  
Single Strain ◽  
Fecal Samples ◽  
Metabolic Functions

Clostridium (C.) difficile-infection (CDI), a nosocomial gastrointestinal disorder, is of growing concern due to its rapid rise in recent years. Antibiotic therapy of CDI is associated with disrupted metabolic function and altered gut microbiota. The use of probiotics as an adjunct is being studied extensively due to their potential to modulate metabolic functions and the gut microbiota. In the present study, we assessed the ability of several single strain probiotics and a probiotic mixture to change the metabolic functions of normal and C. difficile-infected fecal samples. The production of short-chain fatty acids (SCFAs), hydrogen sulfide (H2S), and ammonia was measured, and changes in microbial composition were assessed by 16S rRNA gene amplicon sequencing. The C. difficile-infection in fecal samples resulted in a significant decrease (p < 0.05) in SCFA and H2S production, with a lower microbial alpha diversity. All probiotic treatments were associated with significantly increased (p < 0.05) levels of SCFAs and restored H2S levels. Probiotics showed no effect on microbial composition of either normal or C. difficile-infected fecal samples. These findings indicate that probiotics may be useful to improve the metabolic dysregulation associated with C. difficile infection.

scholarly journals Gut microbiota composition is associated with narcolepsy type 1

2020 ◽  
Vol 7 (6) ◽  
pp. e896
Author(s):  
Alexandre Lecomte ◽  
Lucie Barateau ◽  
Pedro Pereira ◽  
Lars Paulin ◽  
Petri Auvinen ◽  
...  
Keyword(s):  
Community Structure ◽  
Gut Microbiota ◽  
Bacterial Communities ◽  
Beta Diversity ◽  
Alpha Diversity ◽  
Amplicon Sequencing ◽  
Rrna Gene ◽  
Differential Abundance ◽  
Alpha And Beta Diversity

ObjectiveTo test the hypothesis that narcolepsy type 1 (NT1) is related to the gut microbiota, we compared the microbiota bacterial communities of patients with NT1 and control subjects.MethodsThirty-five patients with NT1 (51.43% women, mean age 38.29 ± 19.98 years) and 41 controls (57.14% women, mean age 36.14 ± 12.68 years) were included. Stool samples were collected, and the fecal microbiota bacterial communities were compared between patients and controls using the well-standardized 16S rRNA gene amplicon sequencing approach. We studied alpha and beta diversity and differential abundance analysis between patients and controls, and between subgroups of patients with NT1.ResultsWe found no between-group differences for alpha diversity, but we discovered in NT1 a link with NT1 disease duration. We highlighted differences in the global bacterial community structure as assessed by beta diversity metrics even after adjustments for potential confounders as body mass index (BMI), often increased in NT1. Our results revealed differential abundance of several operational taxonomic units within Bacteroidetes, Bacteroides, and Flavonifractor between patients and controls, but not after adjusting for BMI.ConclusionWe provide evidence of gut microbial community structure alterations in NT1. However, further larger and longitudinal multiomics studies are required to replicate and elucidate the relationship between the gut microbiota, immunity dysregulation and NT1.

scholarly journals Osteopontin-Enriched Algae Modulates the Gut Microbiota Composition in Weaning Piglets Infected with Enterotoxigenic Escherichia Coli (P06-069-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Mei Wang ◽  
Brooke Smith ◽  
Brock Adams ◽  
Miller Tran ◽  
Ryan Dilger ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Gut Microbiota ◽  
Alpha Diversity ◽  
Enterotoxigenic Escherichia Coli ◽  
Farm Animals ◽  
Future Research ◽  
Rrna Gene ◽  
Microbiota Composition ◽  
Wild Type ◽  
Gut Microbiota Composition

Abstract Objectives Enterotoxigenic Escherichia coli (ETEC) are an important cause of diarrhea in human infants and young farm animals. Osteopontin (OPN), a glycoprotein present in high concentration in human milk, has immunomodulatory functions, which could indirectly impact the microbiota. Furthermore, a previous study has shown fecal microbiota composition differs between wild-type and OPN knockout mice. Herein, the effects of OPN-enriched algae on the gut microbiota composition and volatile fatty acid (VFA) concentrations of ETEC-infected piglets were assessed. Methods Naturally-farrowed piglets were sow-reared for 21 days and then randomized to two weaning diets: WT (formula + 1% wild-type algae) or OPN (formula + 1% OPN-enriched algae). On postnatal day (PND) 31, all piglets were infected orally with a live culture of ETEC (1010 colony-forming unit/3 mL dose) daily for three consecutive days. On PND 41, ascending colon (AC) contents were collected. Gut microbiota was assessed by sequencing V3-V4 regions of 16S rRNA gene and VFAs were determined by gas chromatography. Alpha-diversity and VFAs were analyzed using PROC MIXED procedure of SAS. Beta-diversity was evaluated by permutational multivariate analysis of variance (PERMANOVA) and differential abundance analysis on the bacterial genera was performed using DESeq2 package of R. Results Shannon indices were lower in the AC contents of OPN piglets compared to WT piglets. The overall colonic microbiota of OPN piglets differed from that of WT piglets (PERMANOVA P = 0.015). At genus level, OPN-enriched algae increased the abundance of Streptococcus, decreased the abundances of Sutterella, Candidatus Soleaferrea, dga-11 gut group, Rikenellaceae RC9 gut group, Ruminococcaceae UCG-010, unculturedRuminococcaceae, Prevotella 2 and 7 compared to piglets consuming wild-type algae (P < 0. 05). OPN piglets also had higher (P < 0.05) concentrations of acetate, propionate, butyrate and valerate compared to WT. Conclusions In ETEC infected piglets, 1% OPN-enriched algae decreased alpha-diversity and modulated the microbiota composition and VFA profiles compared to 1% WT algae. Other studies have shown that OPN inhibits biofilm formation in vitro, but future research is needed to assess in vivo microbiome-modulation mechanisms. Funding Sources Triton Algae Innovations.

scholarly journals Inbreeding Alters the Gut Microbiota of the Banna Minipig

Animals ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. 2125
Author(s):  
Limin Wei ◽  
Bo Zeng ◽  
Siyuan Zhang ◽  
Feng Li ◽  
Fanli Kong ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Gene Sequencing ◽  
Alpha Diversity ◽  
16S Rrna Gene Sequencing ◽  
Rrna Gene ◽  
Rrna Gene Sequencing ◽  
Isoleucine Metabolism ◽  
Dominant Bacteria ◽  
The Impact ◽  
Predicted Function

The gut microbiota coevolve with the host and can be stably transmitted to the offspring. Host genetics plays a crucial role in the composition and abundance of gut microbiota. Inbreeding can cause a decrease of the host’s genetic diversity and the heterozygosity. In this study, we used 16S rRNA gene sequencing to compare the differences of gut microbiota between the Diannan small-ear pig and Banna minipig inbred, aiming to understand the impact of inbreeding on the gut microbiota. Three dominant bacteria (Stenotrophlomonas, Streptococcus, and Lactobacillus) were steadily enriched in both the Diannan small-ear pig and Banna minipig inbred. After inbreeding, the gut microbiota alpha diversity and some potential probiotics (Bifidobacterium, Tricibacter, Ruminocaccae, Christensenellaceae, etc.) were significantly decreased, while the pathogenic Klebsiella bacteria was significantly increased. In addition, the predicted metagenomic analysis (PICRUSt2) indicated that several amino acid metabolisms (‘‘Valine, leucine, and isoleucine metabolism’’, ‘‘Phenylalanine, tyrosine, and tryptophan biosynthesis’’, ‘‘Histidine metabolism’’) were also markedly decreased after the inbreeding. Altogether our data reveal that host inbreeding altered the composition and the predicted function of the gut microbiome, which provides some data for the gut microbiota during inbreeding.

scholarly journals Interplay of host genetics and gut microbiota underlying the onset and clinical presentation of inflammatory bowel disease

Gut ◽  
2016 ◽  
Vol 67 (1) ◽  
pp. 108-119 ◽  
Author(s):  
Floris Imhann ◽  
Arnau Vich Vila ◽  
Marc Jan Bonder ◽  
Jingyuan Fu ◽  
Dirk Gevers ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Genetic Risk ◽  
Genetic Risk Score ◽  
Alpha Diversity ◽  
Host Genome ◽  
Risk Scores ◽  
Rrna Gene ◽  
Control Analysis ◽  
Healthy Controls ◽  
Healthy Individuals

ObjectivePatients with IBD display substantial heterogeneity in clinical characteristics. We hypothesise that individual differences in the complex interaction of the host genome and the gut microbiota can explain the onset and the heterogeneous presentation of IBD. Therefore, we performed a case–control analysis of the gut microbiota, the host genome and the clinical phenotypes of IBD.DesignStool samples, peripheral blood and extensive phenotype data were collected from 313 patients with IBD and 582 truly healthy controls, selected from a population cohort. The gut microbiota composition was assessed by tag-sequencing the 16S rRNA gene. All participants were genotyped. We composed genetic risk scores from 11 functional genetic variants proven to be associated with IBD in genes that are directly involved in the bacterial handling in the gut: NOD2, CARD9, ATG16L1, IRGM and FUT2.ResultsStrikingly, we observed significant alterations of the gut microbiota of healthy individuals with a high genetic risk for IBD: the IBD genetic risk score was significantly associated with a decrease in the genus Roseburia in healthy controls (false discovery rate 0.017). Moreover, disease location was a major determinant of the gut microbiota: the gut microbiota of patients with colonic Crohn's disease (CD) is different from that of patients with ileal CD, with a decrease in alpha diversity associated to ileal disease (p=3.28×10−13).ConclusionsWe show for the first time that genetic risk variants associated with IBD influence the gut microbiota in healthy individuals. Roseburia spp are acetate-to-butyrate converters, and a decrease has already been observed in patients with IBD.

scholarly journals Gut Microbiota Composition and Metabolomic Profiles of Wild and Captive Chinese Monals (Lophophorus lhuysii) 

2020 ◽  
Author(s):  
Dandan Jiang ◽  
Xin He ◽  
Marc Valitutto ◽  
Li Chen ◽  
Qin Xu ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
High Performance ◽  
Bird Species ◽  
Alpha Diversity ◽  
Integrated Approach ◽  
Fecal Microbiota ◽  
Rrna Gene ◽  
Microbiota Composition ◽  
Metabolomic Profile ◽  
Gut Microbiota Composition

Abstract Background：The Chinese monal (Lophophorus lhuysii) is an endangered bird species, with a wild population restricted to the mountains of southwest China, and only one known captive population in the world. We investigated the fecal microbiota and metabolome of wild and captive Chinese monals to explore differences and similarities in nutritional status and digestive characteristics. An integrated approach combining 16S ribosomal RNA (16S rRNA) gene sequencing and ultra-high performance liquid chromatography (UHPLC) based metabolomics were used to examine the fecal microbiota composition and the metabolomic profile of Chinese monals. Results: The results showed that the alpha diversity of gut microbes in the wild group were significantly higher than that in the captive group and the core bacterial taxa in the two groups showed remarkable differences at phylum, class, order, and family levels. Metabolomic profiling also revealed differences, mainly related to galactose, starch and sucrose metabolism, fatty acid, bile acid biosynthesis and bile secretion. Furthermore, strong correlations of metabolite types and bacterial genus were detected. Conclusions: There were remarkable differences in the gut microbiota composition and metabolomic profile between wild and captive Chinese monals. This study has established a baseline for a normal gut microbiota and metabolomic profile for wild Chinese monals, thus allowing us to evaluate if differences seen in captive organisms have an impact on their overall health and reproduction.

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