scholarly journals Characterization of gut microbiome in mice model of depression with divergent response to escitalopram treatment

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jiajia Duan ◽  
Yu Huang ◽  
Xunmin Tan ◽  
Tingjia Chai ◽  
Jing Wu ◽  
...  

AbstractDepression is a common and heterogeneous mental disorder. Although several antidepressants are available to treat the patients with depression, the factors which could affect and predict the treatment response remain unclear. Here, we characterize the longitudinal changes of microbial composition and function during escitalopram treatment in chronic unpredictable mild stress (CUMS) mice model of depression based on 16 S rRNA sequencing and metabolomics. Consequently, we found that escitalopram (ESC) administration serves to increase the alpha-diversity of the gut microbiome in ESC treatment group. The microbial signatures between responder (R) and non-responder (NR) groups were significantly different. The R group was mainly characterized by increased relative abundances of genus Prevotellaceae_UCG-003, and depleted families Ruminococcaceae and Lactobacillaceae relative to NR group. Moreover, we identified 15 serum metabolites responsible for discriminating R and NR group. Those differential metabolites were mainly involved in phospholipid metabolism. Significantly, the bacterial OTUs belonging to family Lachnospiraceae, Helicobacteraceae, and Muribaculaceae formed strong co-occurring relationships with serum metabolites, indicating alternations of gut microbiome and metabolites as potential mediators in efficiency of ESC treatment. Together, our study demonstrated that the alterations of microbial compositions and metabolic functions might be relevant to the different response to ESC, which shed new light in uncovering the mechanisms of differences in efficacy of antidepressants.

Pathogens ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 463
Author(s):  
Mariusz Sikora ◽  
Albert Stec ◽  
Magdalena Chrabaszcz ◽  
Aleksandra Knot ◽  
Anna Waskiel-Burnat ◽  
...  

(1) Background: A growing body of evidence highlights that intestinal dysbiosis is associated with the development of psoriasis. The gut–skin axis is the novel concept of the interaction between skin diseases and microbiome through inflammatory mediators, metabolites and the intestinal barrier. The objective of this study was to synthesize current data on the gut microbial composition in psoriasis. (2) Methods: We conducted a systematic review of studies investigating intestinal microbiome in psoriasis, using the PRISMA checklist. We searched MEDLINE, EMBASE, and Web of Science databases for relevant published articles (2000–2020). (3) Results: All of the 10 retrieved studies reported alterations in the gut microbiome in patients with psoriasis. Eight studies assessed alpha- and beta-diversity. Four of them reported a lack of change in alpha-diversity, but all confirmed significant changes in beta-diversity. At the phylum-level, at least two or more studies reported a lower relative abundance of Bacteroidetes, and higher Firmicutes in psoriasis patients versus healthy controls. (4) Conclusions: There is a significant association between alterations in gut microbial composition and psoriasis; however, there is high heterogeneity between studies. More unified methodological standards in large-scale studies are needed to understand microbiota’s contribution to psoriasis pathogenesis and its modulation as a potential therapeutic strategy.


2022 ◽  
Vol 8 ◽  
Author(s):  
Shuangyue Li ◽  
Georgios Kararigas

There has been a recent, unprecedented interest in the role of gut microbiota in host health and disease. Technological advances have dramatically expanded our knowledge of the gut microbiome. Increasing evidence has indicated a strong link between gut microbiota and the development of cardiovascular diseases (CVD). In the present article, we discuss the contribution of gut microbiota in the development and progression of CVD. We further discuss how the gut microbiome may differ between the sexes and how it may be influenced by sex hormones. We put forward that regulation of microbial composition and function by sex might lead to sex-biased disease susceptibility, thereby offering a mechanistic insight into sex differences in CVD. A better understanding of this could identify novel targets, ultimately contributing to the development of innovative preventive, diagnostic and therapeutic strategies for men and women.


2019 ◽  
Vol 8 (1) ◽  
pp. 60
Author(s):  
Mohd Baasir Gaisawat ◽  
Chad W. MacPherson ◽  
Julien Tremblay ◽  
Amanda Piano ◽  
Michèle M. Iskandar ◽  
...  

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.


2019 ◽  
Vol 8 (5) ◽  
pp. 693 ◽  
Author(s):  
Yunju Jeong ◽  
Ji-Won Kim ◽  
Hyun Ju You ◽  
Sang-Jun Park ◽  
Jennifer Lee ◽  
...  

Rheumatoid arthritis (RA) is an autoimmune disease characterized by synovial inflammation of the joints and extra-articular manifestations. Recent studies have shown that microorganisms affect RA pathogenesis. However, few studies have examined the microbial distribution of early RA patients, particularly female patients. In the present study, we investigated the gut microbiome profile and microbial functions in early RA female patients, including preclinical and clinically apparent RA cases. Changes in microbiological diversity, composition, and function in each group were analyzed using quantitative insights into microbial ecology (QIIME) and phylogenetic investigation of communities by reconstruction of unobserved states (PICRUSt). The results revealed the dysbiosis due to decreased diversity in the early RA patients compared with healthy subjects. There were significant differences in the microbial distribution of various taxa from phylum to genus levels between healthy subjects and early RA patients. Phylum Bacteroidetes was enriched in early RA patients, while Actinobacteria, including the genus Collinsella, was enriched in healthy subjects. Functional analysis based on clusters of orthologous groups revealed that the genes related to the biosynthesis of menaquinone, known to be derived from gram-positive bacteria, were enriched in healthy subjects, while iron transport-related genes were enriched in early RA patients. Genes related to the biosynthesis of lipopolysaccharide, the gram-negative bacterial endotoxin, were enriched in clinically apparent RA patients. The obvious differences in microbial diversity, taxa, and associated functions of the gut microbiota between healthy subjects and early RA patients highlight the involvement of the gut microbiome in the early stages of RA.


2020 ◽  
Vol 176 (1) ◽  
pp. 1-10 ◽  
Author(s):  
Vicki L Sutherland ◽  
Charlene A McQueen ◽  
Donna Mendrick ◽  
Donna Gulezian ◽  
Carl Cerniglia ◽  
...  

Abstract There is an increasing awareness that the gut microbiome plays a critical role in human health and disease, but mechanistic insights are often lacking. In June 2018, the Health and Environmental Sciences Institute (HESI) held a workshop, “The Gut Microbiome: Markers of Human Health, Drug Efficacy and Xenobiotic Toxicity” (https://hesiglobal.org/event/the-gut-microbiome-workshop) to identify data gaps in determining how gut microbiome alterations may affect human health. Speakers and stakeholders from academia, government, and industry addressed multiple topics including the current science on the gut microbiome, endogenous and exogenous metabolites, biomarkers, and model systems. The workshop presentations and breakout group discussions formed the basis for identifying data gaps and research needs. Two critical issues that emerged were defining the microbial composition and function related to health and developing standards for models, methods and analysis in order to increase the ability to compare and replicate studies. A series of key recommendations were formulated to focus efforts to further understand host-microbiome interactions and the consequences of exposure to xenobiotics as well as identifying biomarkers of microbiome-associated disease and toxicity.


Gut ◽  
2019 ◽  
Vol 69 (3) ◽  
pp. 569-577 ◽  
Author(s):  
Yiran Wei ◽  
Yanmei Li ◽  
Li Yan ◽  
Chunyan Sun ◽  
Qi Miao ◽  
...  

ObjectiveThe significance of the liver-microbiome axis has been increasingly recognised as a major modulator of autoimmunity. The aim of this study was to take advantage of a large well-defined corticosteroids treatment-naïve group of patients with autoimmune hepatitis (AIH) to rigorously characterise gut dysbiosis compared with healthy controls.DesignWe performed a cross-sectional study of individuals with AIH (n=91) and matched healthy controls (n=98) by 16S rRNA gene sequencing. An independent cohort of 28 patients and 34 controls was analysed to validate the results. All the patients were collected before corticosteroids therapy.ResultsThe gut microbiome of steroid treatment-naïve AIH was characterised with lower alpha-diversity (Shannon and observed operational taxonomic units, both p<0.01) and distinct overall microbial composition compared with healthy controls (p=0.002). Depletion of obligate anaerobes and expansion of potential pathobionts including Veillonella were associated with disease status. Of note, Veillonella dispar, the most strongly disease-associated taxa (p=8.85E–8), positively correlated with serum level of aspartate aminotransferase and liver inflammation. Furthermore, the combination of four patients with AIH-associated genera distinguished AIH from controls with an area under curves of approximately 0.8 in both exploration and validation cohorts. In addition, multiple predicted functional modules were altered in the AIH gut microbiome, including lipopolysaccharide biosynthesis as well as metabolism of amino acids that can be processed by bacteria to produce immunomodulatory metabolites.ConclusionOur study establishes compositional and functional alterations of gut microbiome in AIH and suggests the potential for using gut microbiota as non-invasive biomarkers to assess disease activity.


2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 1188-1188
Author(s):  
Sina Ullrich ◽  
Kerstin Thriene ◽  
Nadine Binder ◽  
Lena Amend ◽  
Till Strowig ◽  
...  

Abstract Objectives The effects of fermented foods on the gut microbiome are of great interest, yet evidence regarding its potential to increase gut microbial diversity, a measure likely associated with health, is lacking. Therefore, we analyzed the microbial composition (bacteria and yeasts) of commercially available fermented vegetables. Furthermore, we conducted a pilot study to assess the feasibility of studying effects of regular consumption of fermented vegetables on the gut microbiome. Methods Six healthy male volunteers (age: 25.5 ± 2.9yrs, BMI: 24.3 ± 1.2kg/m2) participated in a randomized crossover trial, with two 2-week intervention phases each of which was preceded by a 2-week washout phase. Participants consumed 150g/d of either sauerkraut (intervention 1) or a variety of six different fermented vegetables (intervention 2). We used 16S rRNA sequencing to assess the effects of each dietary regime on the composition, diversity and dynamics of the gut microbiome, as well as the composition and diversity of the fermented vegetable microbiome. Results Lactobacillus was the dominant genus in all fermented vegetables; still, the alpha diversity, richness and evenness of the microbiota differed substantially among the different products. Among our study participants, we observed an increase in alpha diversity (Shannon index) after both, consumption of sauerkraut (pre intervention: 3.31 ± 0.74, post intervention: 3.58 ± 0.68) and the selection of fermented vegetables (pre: 3.60 ± 0.93, post: 3.84 ± 0.81). However, the results did not reach statistical significance, due to the high inter- and intra-individual variability as evaluated by beta diversity of the gut microbial communities. Conclusions A longer-term intervention study with fermented vegetables and/or sauerkraut seems feasible. Consumption of fermented vegetables appears to increase the diversity of the gut microbiome, even after a relatively short period of time. However, further studies with a larger sample size are warranted to verify our observations. Funding Sources Institutional budget.


Microbiome ◽  
2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Congying Chen ◽  
Shaoming Fang ◽  
Hong Wei ◽  
Maozhang He ◽  
Hao Fu ◽  
...  

Abstract Background Excessive fat accumulation of pigs is undesirable, as it severely affects economic returns in the modern pig industry. Studies in humans and mice have examined the role of the gut microbiome in host energy metabolism. Commercial Duroc pigs are often fed formula diets with high energy and protein contents. Whether and how the gut microbiome under this type of diet regulates swine fat accumulation is largely unknown. Results In the present study, we systematically investigated the correlation of gut microbiome with pig lean meat percentage (LMP) in 698 commercial Duroc pigs and found that Prevotella copri was significantly associated with fat accumulation of pigs. Fat pigs had significantly higher abundance of P. copri in the gut. High abundance of P. copri was correlated with increased concentrations of serum metabolites associated with obesity, e.g., lipopolysaccharides, branched chain amino acids, aromatic amino acids, and the metabolites of arachidonic acid. Host intestinal barrier permeability and chronic inflammation response were increased. A gavage experiment using germ-free mice confirmed that the P. copri isolated from experimental pigs was a causal species increasing host fat accumulation and altering serum metabolites. Colon, adipose tissue, and muscle transcriptomes in P. copri-gavaged mice indicated that P. copri colonization activated host chronic inflammatory responses through the TLR4 and mTOR signaling pathways and significantly upregulated the expression of the genes related to lipogenesis and fat accumulation, but attenuated the genes associated with lipolysis, lipid transport, and muscle growth. Conclusions Taken together, the results proposed that P. copri in the gut microbial communities of pigs fed with commercial formula diets activates host chronic inflammatory responses by the metabolites through the TLR4 and mTOR signaling pathways, and increases host fat deposition significantly. The results provide fundamental knowledge for reducing fat accumulation in pigs through regulating the gut microbial composition.


Animals ◽  
2019 ◽  
Vol 9 (10) ◽  
pp. 713 ◽  
Author(s):  
Jipeng Jin ◽  
Liping Zhang ◽  
Jianlei Jia ◽  
Qian Chen ◽  
Zan Yuan ◽  
...  

The jejunum is the primary organ for digestion and nutrient absorption in mammals. The development of the jejunum in suckling piglets directly affects their growth performance post-weaning. The jejunum microbiome plays an important role in proliferation, metabolism, apoptosis, immune, and homeostasis of the epithelial cells within the organ. The composition and diversity of the gut microbiome is susceptible to the protein composition of the diet. Therefore, the effects of maternal low-protein diets on piglets’ intestinal microbial structure and function have become a hot topic of study. Herein, a maternal low-protein diet was formulated to explore the effects on jejunum microbiome composition and metabolic profiles in Bamei suckling piglets. Using 16S ribosomal RNA (16S rRNA) sequencing in conjunction with bioinformatics analysis, 21 phyla and 297 genera were identified within the gut microflora. The top 10 phyla and 10 genera are within the gut bacteria. Next, KEGG analysis showed that the low-protein diet significantly increased the gut microbial composition, transport and catabolism, immune system, global and overview maps, amino acid metabolism, metabolism of cofactors and vitamins, endocrine system, biosynthesis of other secondary metabolites, signal transduction, environmental adaptation, and cell motility. Taken together, low-protein diets do not appear to affect the reproductive performance of Bamei sows but improved the gut microbiome of the suckling piglets as well as reduced the probability of diarrhea. The data presented here provide new insights on the dietary protein requirements to support the Huzhu Bamei pig industry.


2020 ◽  
Vol 3 (Supplement_1) ◽  
pp. 137-138
Author(s):  
N Eissa ◽  
A Diarra ◽  
H Hussein ◽  
C N Bernstein ◽  
J Ghia

Abstract Background Ulcerative colitis (UC)is characterized by distinct changes in the gut microbiome and elevated chromogranin-A (CHGA) level, which seem to be a relevant pathogenetic mechanism.CHGA, a prohormone produced by enterochromaffin (EC) cells and cleaved into several bioactive peptides, regulates experimental colonic inflammation. In the rodent, intra-rectal infusion of catestatin, a Chga-derived peptide, alters the distal colonic microbial composition. However, the interplay between CHGA, as a pro-hormone, and the gut microbiome remains elusive. Aims in homoeostatic and pathophysiologic conditions, we investigated the functional consequences of the lack of Chgaon the distal colonic microbiota. Methods Acute colitis (5 % dextran sulfate sodium [DSS], 5 days) was induced in Chga-C57BL/6-deficient (Chga-/-) and wild-type (Chga+/+)mice. Feces and mucosa-associated microbiota (MAM) samples were collected and the V4 region of 16s rRNA was subjected to Miseq Illumina sequencing. Alpha diversity was calculated using Shannon’s diversity index. OTU abundances were summarized using the Bray-Curtis index and non-metric multidimensional scaling (NMDS) analysis to visualize microbiome similarities and a permutational analysis of variance (PERMANOVA) to test the significance of groups were performed respectively. Results In non-colitic homoeostatic condition, the absence of Chga (Chga-/) significantly increased the bacterial richness and modified the bacterial community composition at the genera level between the groups, represented by increased abundance of Lactobacillus species and reduced abundance of Helicobacter& Oscillospira species compared to Chga+/+mice in fecal and colonic MAM. Moreover, the absence of Chga (Chga-/-) resulted in a significant change in the alpha-diversity of fecal and colonic MAM compared to Chga+/+mice. DSS induced-colitis resulted in a significant microbial dysbiosis in Chga+/+mice, however, deletion of Chgaprotected against DSS-induced colitis and reduced the microbial dysbiosis, reduced the family of Rikenellaceaeand maintained the abundance of Bacteroides species, compared to wild-type (Chga+/+). Conclusions The lack of CHGA regulates the biodiversity and the composition of the colonic gut microbiota suggesting a cross-talk between the EC cell and the microbiome. Therefore, targeting CHGA could provide a novel therapeutic strategy by regulating the gut microbiome in physiological and pathophysiological conditions. Funding Agencies CIHR


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