scholarly journals Gut Microbiota and Related Metabolites Were Disturbed in Ulcerative Colitis and Partly Restored After Mesalamine Treatment

2021 ◽  
Vol 11 ◽  
Author(s):  
Liang Dai ◽  
Yingjue Tang ◽  
Wenjun Zhou ◽  
Yanqi Dang ◽  
Qiaoli Sun ◽  
...  

Mesalamine has been well used in the improvement of ulcerative colitis (UC) in clinics, however, the underlying mechanisms were not well illustrated. To explore its efficacy from the perspective of gut microbiota and related metabolites, we employed 16S rRNA sequencing and metabolomics approaches in stool samples across 14 normal healthy controls (NC group), 10 treatment-naïve UC patients (UC group) and 14 UC patients responded to mesalamine treatment (mesalamine group). We noted that the gut microbiota diversity and community composition were remarkably perturbed in UC group and partially restored by mesalamine treatment. The relative abundance of 192 taxa in genus level were significantly changed in UC group, and 168 genera were significantly altered after mesalamine intervention. Meanwhile, a total of 127 metabolites were significantly changed in UC group and 129 metabolites were significantly altered after mesalamine treatment. Importantly, we observed that many candidates including 49 genera (such as Escherichia-shigella, Enterococcus and Butyricicoccus) and 102 metatoblites (such as isoleucine, cholic acid and deoxycholic acid) were reversed by mesalamine. Spearman correlation analysis revealed that most of the candidates were significantly correlated with Mayo score of UC, and the relative abundance of specific genera were significant correlated with the perturbation of metabolites. Pathway analysis demonstrated that genera and metabolites candidates were enriched in many similar molecular pathways such as amino acid metabolism and secondary metabolites biosynthesis. Importantly, ROC curve analysis identified a gut microbiota signature composed of five genera including Escherichia-Shigella, Streptococcus, Megamonas, Prevotella_9 and [Eubacterium] _coprostanoligenes _group which might be used to distinguish UC group from both NC and mesalamine group. In all, our results suggested that mesalamine might exert a beneficial role in UC by modulating gut microbiota signature with correlated metabolites in different pathways, which may provide a basis for developing novel candidate biomarkers and therapeutic targets of UC.

2020 ◽  
Vol 11 (1) ◽  
pp. 124-133
Author(s):  
Hao Li ◽  
Xiaohui Zhang ◽  
Dengdeng Pan ◽  
Yongqiang Liu ◽  
Xuebing Yan ◽  
...  

AbstractObjectiveThe aim of this study is to investigate the dysbiosis characteristics of gut microbiota in patients with cerebral infarction (CI) and its clinical implications.MethodsStool samples were collected from 79 CI patients and 98 healthy controls and subjected to 16S rRNA sequencing to identify stool microbes. Altered compositions and functions of gut microbiota in CI and its correlation with clinical features were investigated. Random forest and receiver operating characteristic analysis were used to develop a diagnostic model.ResultsMicrobiota diversity and structure between CI patients and healthy controls were overall similar. However, butyrate-producing bacteria (BPB) were significantly reduced in CI patients, while lactic acid bacteria (LAB) were increased. Genetically, BPB-related functional genes were reduced in CI patients, whereas LAB-related genes were enhanced. The interbacterial correlations among BPB in CI patients were less prominent than those in healthy controls. Clinically, BPB was negatively associated with the National Institutes of Health Stroke Scale (NIHSS), while LAB was positively correlated with NIHSS. Both BPB and LAB played leading roles in the diagnostic model based on 47 bacteria.ConclusionsThe abundance and functions of BPB in CI patients were significantly decreased, while LAB were increased. Both BPB and LAB displayed promising potential in the assessment and diagnosis of CI.


Metabolites ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 482
Author(s):  
Jae-Kwon Jo ◽  
Seung-Ho Seo ◽  
Seong-Eun Park ◽  
Hyun-Woo Kim ◽  
Eun-Ju Kim ◽  
...  

Obesity can be caused by microbes producing metabolites; it is thus important to determine the correlation between gut microbes and metabolites. This study aimed to identify gut microbiota-metabolomic signatures that change with a high-fat diet and understand the underlying mechanisms. To investigate the profiles of the gut microbiota and metabolites that changed after a 60% fat diet for 8 weeks, 16S rRNA gene amplicon sequencing and gas chromatography-mass spectrometry (GC-MS)-based metabolomic analyses were performed. Mice belonging to the HFD group showed a significant decrease in the relative abundance of Bacteroidetes but an increase in the relative abundance of Firmicutes compared to the control group. The relative abundance of Firmicutes, such as Lactococcus, Blautia, Lachnoclostridium, Oscillibacter, Ruminiclostridium, Harryflintia, Lactobacillus, Oscillospira, and Erysipelatoclostridium, was significantly higher in the HFD group than in the control group. The increased relative abundance of Firmicutes in the HFD group was positively correlated with fecal ribose, hypoxanthine, fructose, glycolic acid, ornithine, serum inositol, tyrosine, and glycine. Metabolic pathways affected by a high fat diet on serum were involved in aminoacyl-tRNA biosynthesis, glycine, serine and threonine metabolism, cysteine and methionine metabolism, glyoxylate and dicarboxylate metabolism, and phenylalanine, tyrosine, and trypto-phan biosynthesis. This study provides insight into the dysbiosis of gut microbiota and metabolites altered by HFD and may help to understand the mechanisms underlying obesity mediated by gut microbiota.


2020 ◽  
Vol 8 (10) ◽  
pp. 1579
Author(s):  
Deng Lin ◽  
Ran Wang ◽  
Junjie Luo ◽  
Fazheng Ren ◽  
Zhenglong Gu ◽  
...  

The diversity of the human gut microbiota constitutes a fundamental health indicator of different populations. The relative importance of geographical location and ethnicity on the gut microbiota, however, has not been previously addressed. Due to unique ethnic distributions across China, we recruited distinct minority ethnic groups, including Han populations, in each of the seven cities that were explored in this study. We investigated the gut microbiota of 394 healthy subjects (14 groups) from these seven different cities using 16S rRNA sequencing. Our results indicated that both geographical location and ethnicity were major factors. However, geographical location exhibited greater influence than ethnicity on both the composition and diversity of the gut microbiota. In addition, a total of 15 shared biomarkers at the genus level were identified in three distinct locations, including seven in Inner Mongolia, seven in Xinjiang and one in Gansu. Furthermore, 65 unique biomarkers were found in 14 population groups, which indicated specific communities in different populations. Based on the gut microbiota species, two main enterotypes—namely Prevotella (ETP) and Bacteroides (ETB), which consist of Prevotella and Bacteroides as the core bacterial genus, were observed in Chinese populations. Our unique experimental design using the same ethnic group—Han, as a control in different locations, enables delineating the importance of geographical location and ethnicity on the gut microbiota, and provides the fundamental characteristics of gut microbiota diversity in Chinese populations.


Nutrients ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 2837
Author(s):  
Hiromi Tanabe ◽  
Kenichi Sakurai ◽  
Yumiko Nakanishi ◽  
Tamotsu Kato ◽  
Yohei Kawasaki ◽  
...  

Chemokine (C-C motif) ligand 17 (CCL17) is a pro-allergic factor: high CCL17 levels in cord blood (CB) precede later allergic predisposition. Short-chain fatty acid (SCFA) treatment during pregnancy has been shown to protect mouse pups against allergic diseases. The maternal microbial metabolome during pregnancy may affect fetal allergic immune responses. We therefore examined the associations between CB CCL17 and gut SCFA levels in healthy pregnant Japanese women. CB CCL17 serum levels at birth, and maternal non-specific IgE levels in maternal sera at 32 weeks of gestation were measured. Maternal stool samples were collected at 12 (n = 59) and 32 (n = 58) weeks of gestation for gut microbiota analysis, based on barcoded 16S rRNA sequencing and metabolite levels. The CB CCL17 levels correlated negatively with butyrate concentrations and positively with isobutyrate at 12 weeks; CB CCL17 correlated positively with valerate and lactate at 32 weeks. Similarly, butyrate levels correlated negatively with maternal non-specific IgE levels, whereas the lactate concentration correlated positively with IgE levels. At 32 weeks, the Shannon diversity index (SDI) of Firmicutes and Proteobacteria correlated negatively with CB CCL17 levels, while those of the total microbiota correlated positively with the CB CCL17 levels. These metabolites may alter fetal immune responses. This study provides the first link between maternal metabolites during pregnancy and the risk of allergic diseases in human offspring.


2021 ◽  
Author(s):  
LINGLING WANG ◽  
Haobin Yao ◽  
Tereasa Tong ◽  
KS Lau ◽  
Suet Yi Leung ◽  
...  

Abstract Background: Short-term antibiotics exposure is associated with alterations in microbiota and antibiotic resistance genes (ARGs) in the human gut. While antibiotics are critical in the successful eradication of Helicobacter pylori, the short-term and long-term impacts on the composition and quantity of antibiotics resistance genes after H. pylori eradication is unclear. This study used whole genome shotgun metagenomic of stool samples to characterize the gut microbiota and ARGs, before and after H. pylori eradication therapy. Results: Forty-four H. pylori-infected patients were recruited including 21 treatment naïve patients who received clarithromycin-based triple therapy (CLA group) and 23 patients who failed previous therapies, in which 10 received levofloxacin-based quadruple therapy [LEVO group] and 13 received other combinations [OTHER group] in the current study. Stool samples were collected at baseline (before current treatment), 6-week and 6-month after eradication therapy. At baseline, there was only a slight difference among the three groups on ARGs and gut microbiota. After eradication therapy, there was a transient but significant increase in gut ARGs 6-week post-therapy, among which the LEVO group had the most significant ARGs alteration compared to other two groups. For treatment naïve patients, those with higher ARG richness and ErmF abundance were prone to fail CLA eradication. For gut microbiota, the bacteria richness decreased at 6-week and there was a significant difference in microbiota community among the three groups at 6-week. Conclusions: Our findings demonstrated the dynamic alterations in gut microbiota and ARGs induced by different eradication therapies, which could influence the choices of antibiotics in eradication therapy.


Molecules ◽  
2018 ◽  
Vol 23 (11) ◽  
pp. 2832 ◽  
Author(s):  
Dan Cheng ◽  
Hongsheng Chang ◽  
Suya Ma ◽  
Jian Guo ◽  
Gaimei She ◽  
...  

Tiansi Liquid is a traditional Chinese herbal medicine used to treat depression; however, the underlying mechanisms remain unclear. Here, we examined the effect of Tiansi Liquid in a rat model of hydrocortisone-induced depression using behavioral testing, 16S rRNA high-throughput pyrosequencing and high-performance liquid chromatography-mass spectrometry-based metabolomics of the tryptophan (TRP)–kynurenine (KYN) pathway. Tiansi Liquid significantly improved the sucrose preference and exploratory behavior of the depressive rats. The richness of intestinal mucosa samples from the model (depressive) group tended to be higher than that from the control group, while the richness was higher in the Tiansi Liquid-treated group than in the model group. Tiansi Liquid increased the relative abundance of some microbiota (Ruminococcaceae, Lactococcus, Lactobacillus, Lachnospiraceae_NK4A136_group). Metabolomics showed that Tiansi Liquid reduced the levels of tryptophan 2,3 dioxygenase, indoleamine 2,3-dioxygenase, quinoline and the KYN/TRP ratio, while increasing kynurenic acid and 5-HT levels. Correlation analysis revealed a negative relationship between the relative abundance of the Lachnospiraceae_NK4A136_group and quinoline content. Collectively, these findings suggest that Tiansi Liquid ameliorates depressive symptoms in rats by modulating the gut microbiota composition and metabolites in the TRP–KYN pathway.


2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S240-S240
Author(s):  
O K Bakkaloglu ◽  
T Eskazan ◽  
S Bozcan ◽  
S Yıldırım ◽  
E A Kurt ◽  
...  

Abstract Background Although faecal calprotectin can predict mucosal remission in ulcerative colitis, the CRP level in this context is insufficient and frequently stay under the current cut off level. While some patients with active mucosal disease have normal CRP levels most patients in mucosal remission have much lower CRP levels. The aim of this study is to define CRP cut off levels in the prediction of mucosal remission, considering both extensiveness and severity, in ulcerative colitis. Methods We retrospectively reviewed colonoscopy reports of ulcerative colitis patients (who are not on any steroid treatment at that time) which were performed between December 2016 and March 2019 and also their CRP levels which were obtained at the same week of the colonoscopy examination. We excluded the data of patients with any other possible cause of inflammation or infection at the time of laboratory assessment. Degree of mucosal disease at colonoscopy was evaluated according to endoscopic Mayo score. Mucosal remission was defined as endoscopic Mayo score 0 or 1. The extent of mucosal inflammation was classified according to Montreal classification. The CRP level with optimal sensitivity and specificity for mucosal remission prediction was assessed by ROC curve analysis and positive and negative predictive values were also calculated. Results A total of 331 colonoscopy reports of 260 patients (122 m, 138 f) were involved in this study. There were no significant differences between ages of patients when compared with ex, and Montreal classification and we did not find any correlation between age and CRP levels. Sensitivity, specificity, positive predictive value and negative predictive values for 5 mg/l, 3 mg /l and 2 mg/l are summarised in Table 1. CRP levels which predict Mayo 0 disease, mucosal remission (Mayo 0–1) and Mayo 3 disease are shown in Table 2. At the ROC curve analysis, we found that CRP level of approximately 2.9 mg/l can predict mucosal remission with a 77% sensitivity and % 80 specificity in all examinations without grouping into a separate segmental disease. For subgroups with Montreal E1, E2 and E3 ROC curve analysis suggested 1,8 mg/l (sn. 84%, sp. 90%), 2,7 mg/l (sn. 75%, sp. 75%) and 3 mg/l (sn. 80%, sp. 80%) CRP levels can be used for prediction of mucosal remission respectively (Table 3). It is important to emphasise that 30% of all patients with Mayo 3 colonoscopy and further 23% of patients with Montreal E3–Mayo 3 activity have CRP levels below the regular cut-off value of 5 mg/l. Conclusion CRP cut-off level of approximately 2.9 mg/l can predict mucosal remission in ulcerative colitis better than standard cut-off of 5 mg/l which has a low positive predictive value and specificity even at extended and active mucosal disease.


Nutrients ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 2710
Author(s):  
Amanda Cuevas-Sierra ◽  
Fermín I. Milagro ◽  
Paula Aranaz ◽  
Jose Alfredo Martínez ◽  
José I. Riezu-Boj

Ultra-processed foods (UPFs) consumption could affect gut microbiota diversity and profile. We aimed to evaluate the effects of UPFs on microbiota, considering the role of sex. The consumption of UPFs (using NOVA criteria) was assessed with a validated 137-item food-frequency questionnaire. Participants (n = 359) were classified into less than three servings per day (n = 96) of UPFs and more than five (n = 90). Women and men were subclassified following the same criteria. 16S rRNA sequencing was performed from DNA fecal samples, and differences in microbiota were analyzed using EdgeR. The relationship between UPFs and bacteria was assessed by Spearman correlation and comparison of tertiles of consumption. Women who consumed more than five servings/day of UPFs presented an increase in Acidaminococcus, Butyrivibrio, Gemmiger, Shigella, Anaerofilum, Parabacteroides, Bifidobacterium, Enterobacteriales, Bifidobacteriales and Actinobacteria and a decrease in Melainabacter and Lachnospira. Bifidobacterium, Bifidobacteriales and Actinobacteria was positively associated with pizza and Actinobacteria with industrially processed dairy in women. Men who consumed more than five servings/day presented an increase of Granulicatella, Blautia, Carnobacteriaceae, Bacteroidaceae, Peptostreptococcaceae, Bacteroidia and Bacteroidetes and a decrease of Anaerostipes and Clostridiaceae. Bacteroidia and Bacteroidetes correlated positively with industrially processed meat. This study suggests that UPFs may affect microbiota composition differently in women and men.


Author(s):  
Ming Zhang ◽  
Aoqiang Li ◽  
Qifang Yang ◽  
Jingyi Li ◽  
Lihua Wang ◽  
...  

It was recently shown that the gut microbiota of both depression patients and depression model animals is significantly altered, suggesting that gut microbes are closely related to depression. Here, we investigated the effects of Sophora alopecuroides L.-derived alkaloids on the gut microbiota of mice with depression-like behaviors. We first established a mouse model of depression via chronic unpredictable mild stress (CUMS) and detected changes in depression-like behaviors and depression-related indicators. Simultaneously, 16S rRNA sequencing was performed to investigate gut microbiota changes. Sophora alopecuroides L.-derived alkaloids improved depression-like behaviors and depression-related indicators in mice. The alkaloids decreased the gut microbiota diversity of CUMS mice and depleted intestinal differentially abundant “harmful” microbiota genera. Spearman analysis showed that there is a certain correlation between the differential microbiota (Lactobacillus, Helicobacter, Oscillospira, Odoribacter, Mucispirillum, Ruminococcus), depression-like behaviors, and depression-related indicators. Combined with the predictive analysis of gut microbiota function, these results indicate that alkaloids improve depression in mice through modulating gut microbiota.


2021 ◽  
Author(s):  
Henghui Li ◽  
Xu Zhang ◽  
Rui Chen ◽  
Kai Cheng ◽  
Zhibin Ning ◽  
...  

Pediatric ulcerative colitis (UC) is a distinct type of inflammatory bowel disease with severe disease activity and rapid progression, which can lead to detrimental life-long consequences. The pathogenesis of pediatric UC remains unclear, although dysbiosis of the gut microbiota has been considered an important factor. In this study, we used mass spectrometry-based glycomic approaches to examine the N-glycans that were associated with the intestinal mucosal-luminal interface microbiota cells of treatment-naive pediatric UC or control patients. We observed abundant paucimannosidic and other truncated N-glycans that were associated with the microbiota and found that the pediatric UC microbiota samples contained significantly higher levels of these atypical N-glycans compared to those of controls. This study indicates that intestinal N-glycans may be used as novel UC biomarker candidates and the aberrant metabolism of glycans by gut microbiota may be involved in the pathogenesis of UC in children.


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