Identification of a novel interplay between intestinal bacteria and metabolites in Chinese patients with IgA nephropathy via integrated microbiome and metabolome approaches

Wu, Hongwei; Tang, Donge; Zheng, Fengping; Li, Shanshan; Zhang, Xinzhou; Li, Yin; Liu, Fanna; Dai, Yong

doi:10.21037/atm-20-2506

Cited by 17 publications

(38 citation statements)

References 45 publications

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“…Besides, we also found an elevation of Streptococcus in both active and inactive MPA groups. Elevated intestinal Streptococcus has been described in patients with IgA nephropathy (47). Frequent mucosal carriage of Streptococcus may induce a glycosylation deficiency in IgA1, which is an important pathogenetic mechanism of IgA nephrology (48).…”

Section: Discussionmentioning

confidence: 99%

The gut microbiome in microscopic polyangiitis with kidney involvement: common and unique alterations, clinical association and values for disease diagnosis and outcome prediction

Jin

Chen

et al. 2021

Ann Transl Med

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Background: Microscopic polyangiitis (MPA) is an autoimmune disease characterized by frequent kidney involvement. Imbalance of intestinal flora has been found implicated in multiple immune-mediated disorders. However, the profiling and the role of the gut microbiome in MPA remains unclear.Methods: We performed 16S rRNA amplicon sequencing on fecal samples from 71 MPA patients with kidney involvement (35 at incipient active stage, 36 at remissive stage) and 34 healthy controls (HCs).Microbial diversity and abundance were compared among the three cohorts. The correlation between altered microbes and clinical indices were investigated. Two random forest models based on the profiling of the gut microbiome were constructed for the diagnosis of MPA.Results: Two α-diversity indices, including Simpson and Shannon index, were decreased in MPA patients (P<0.001), especially in those with active disease (P=0.001). β-diversity analysis showed biased microbial composition among the three groups. Genus Actinomyces and Streptococcus were more abundant in both MPA cohorts than those in HCs, while genus Subdoligranulum, Eubacterium hallii, Ruminococcaceae UCG013, Eubacterium ventriosum, Dorea and Butyricicoccus were more abundant in HCs than those in both MPA cohorts. All the 6 genera with decreased abundance belong to short-chain fatty acids (SCFA)-producing taxons. Besides, 1 and 2 operational taxonomic units (OTUs) were enriched in patients with active MPA who needed dialysis at sampling and in patients who progressed to end-stage renal disease during follow up, respectively. Furthermore, the model for diagnosis of MPA incorporated 6 OTU markers and achieved an AUC of 93.45% (95% CI, 88.15-98.74%). Similarly, the model for predicting disease activity incorporated 11 OTU markers and achieved an AUC of 90.71% (95% CI, 82.49-98.94%).Conclusions: Alteration of intestinal flora existed in MPA patients with kidney involvement and was characterized by increased abundance of genus Actinomyces and Streptococcus and decreased abundance of 6 SCFA-producing genera. Gut microbial profiling combined with machining-learning methods showed potentials for diagnosing MPA and predicting disease activity.

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Section: Discussionmentioning

confidence: 99%

The gut microbiome in microscopic polyangiitis with kidney involvement: common and unique alterations, clinical association and values for disease diagnosis and outcome prediction

Jin

Chen

et al. 2021

Ann Transl Med

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“…A total of 269 studies were retrieved from PubMed, Embase, WOS, CNKI, Cochrane Library, and , 11 studies were finally included after eliminating duplications and screening in accordance with the pre-designed criteria ( De Angelis et al., 2014 ; Dong et al., 2020 ; Hu et al., 2020 ; Zhong et al., 2020 ; Chai et al., 2021 ; He et al., 2021 ; Sugurmar et al., 2021 ; Tian et al., 2021 ; Weng et al., 2021 ; Wu et al., 2021 ; Ya et al., 2021 ). The detailed process of study identification is displayed in the PRISMA flow diagram ( Figure 1 ).…”

Section: Resultsmentioning

confidence: 99%

“…The characteristics of included studies are described in Table 1 , which were 11 cross-sectional studies published between 2014 and 2021, yielding 652 individual fecal samples for microbiome analyses. Nine studies were conducted in China ( Dong et al., 2020 ; Hu et al., 2020 ; Zhong et al., 2020 ; Chai et al., 2021 ; He et al., 2021 ; Tian et al., 2021 ; Weng et al., 2021 ; Wu et al., 2021 ; Ya et al., 2021 ), one in Malaysia ( Sugurmar et al., 2021 ), and one in Italy ( De Angelis et al., 2014 ). All the gut microflora analyses were compared between patients with IgAN and healthy controls, who were adjusted with age and gender, additionally, body mass index (BMI) and dietary habits were also matched in seven studies ( Dong et al., 2020 ; Hu et al., 2020 ; Chai et al., 2021 ; He et al., 2021 ; Sugurmar et al., 2021 ; Weng et al., 2021 ; Wu et al., 2021 ) and four studies ( Hu et al., 2020 ; Zhong et al., 2020 ; Sugurmar et al., 2021 ; Wu et al., 2021 ).…”

Section: Resultsmentioning

confidence: 99%

“…Fresh stool samples were collected in containers and immediately stored at -80°C [five studies described “sterile” ( De Angelis et al., 2014 ; Hu et al., 2020 ; Tian et al., 2021 ; Weng et al., 2021 ; Zhong et al., 2020 )]. The amplified region of 16S rRNA gene (16S) was V3-V4 in nine studies ( Dong et al., 2020 ; Hu et al., 2020 ; Zhong et al., 2020 ; Chai et al., 2021 ; He et al., 2021 ; Sugurmar et al., 2021 ; Tian et al., 2021 ; Wu et al., 2021 ; Weng et al., 2021 ) and V1-V3 in one study ( De Angelis et al., 2014 ), one study did not specify the amplified region ( Ya et al., 2021 ). Sequencing platforms from Illumina were used in nine studies ( Dong et al., 2020 ; Hu et al., 2020 ; Zhong et al., 2020 ; He et al., 2021 ; Sugurmar et al., 2021 ; Tian et al., 2021 ; Weng et al., 2021 ; Wu et al., 2021 ; Ya et al., 2021 ).…”

Section: Resultsmentioning

confidence: 99%

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Gut Microbiome Characteristics in IgA Nephropathy: Qualitative and Quantitative Analysis from Observational Studies

Han

et al. 2022

Front. Cell. Infect. Microbiol.

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BackgroundRecent data indicate the importance of gut-kidney axis in the pathogenesis of Immunoglobulin A nephropathy (IgAN). Growing evidence suggests the alterations of diversity and composition of gut microbiome among patients with IgAN, however, the details are not yet fully understood.MethodsEligible studies comparing the gut microbiome between patients with IgAN and non-IgAN individuals were systematically searched from PubMed, Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure, and ClinicalTrials.gov. The primary outcomes were alpha- and beta-diversity, and the differences in gut microbiota composition between patients with IgAN and non-IgAN persons. Qualitative analysis and meta-analysis were performed according to available data.ResultsEleven cross-sectional studies, including 409 patients with IgAN and 243 healthy controls, were enrolled. No significant differences in the diversity and enrichment of gut bacteria were found between IgAN and healthy individuals, whereas the beta-diversity consistently showed significant microbial dissimilarities among the two groups. Firmicutes, Bacteroidetes, Actinobacteria, Proteobacteria, Fusobacteria, and Verrucomicrobia were the dominant phyla, however, no significant differences were found between IgAN patients and healthy controls at the phylum level. The genera, Streptococcus and Paraprevotella showed a higher proportion in patients with IgAN compared to healthy individuals, whereas Fusicatenibacter showed a lower abundance according to meta-analysis. Qualitative analyses suggested that Escherichia-Shigella might be increased in IgAN patients; the genera, Clostridium, Prevotella 9,and Roseburia, members of Ruminococcaceae and Lachnospiraceae families, were likely to have decreased abundances in patients with IgAN compared to healthy individuals.ConclusionGut microbiota dysbiosis was demonstrated in IgAN, which might be involved in the pathogenesis of IgAN. Further studies are needed to confirm the findings of this study, due to the substantial heterogeneity.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/, identifier PROSPERO (CRD42022304034).

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“…Paired-end reads obtained by Illumina sequencing were merged into specific tags based on their overlapping information by FLASH software (v1.2.7). After removing the low-quality tags by Trimmomatic software (v0.33), we used UCHIME v4.2 to filter the chimeric sequences of the clean tags (9).…”

Section: S Rrna Sequencingmentioning

confidence: 99%

Metabolic Dysfunctions of Intestinal Fatty Acids and Tryptophan Reveal Immuno-Inflammatory Response Activation in IgA Nephropathy

Tang

Yun

et al. 2022

Front. Med.

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BackgroundImmunoglobulin A nephropathy (IgAN) is the most common form of primary glomerulonephritis. Although an important link between intestinal metabolites and immune activity is widely established, the metabolic profile of IgAN is still poorly understood, which severely limits the mechanistic studies and therapy of IgAN.MethodsThe diversity of intestinal flora and relative abundance of metabolites in IgAN patients and healthy subjects were measured by 16s ribosomal RNA gene sequencing combined with liquid chromatography tandem-mass spectrometry. The levels of serum Gd-IgA1, IL-6, IL-10, IL-22, and TNF-a were tested by ELISA. We employed the tryptophan-targeted UHPLC-MRM-MS approach to assess the content of tryptophan metabolites quantitatively.ResultsIntestinal fatty acid levels, mainly unsaturated fatty acids, were observed to be dramatically decreased in IgAN patients. Disorders in linoleic acid and arachidonic acid metabolism, metabolic imbalances of anti-/pro- inflammatory fatty acid metabolites, and intestinal AhR signaling deficiency might reflect the damage of the intestinal mucosal barrier in IgAN patients. In addition, we found that high levels of Gd-IgA1, IL-22, and TNF-α were associated with the activity of the tryptophan-kynurenine metabolic pathway, as well as lower levels of 3-indolepropionic acid. 3-indolepropionic acid, kynurenine, and indoleacrylic acid had synergistic effects on regulating immuno-inflammatory responses in IgAN patients.ConclusionsThe metabolic characteristic of fatty acids and tryptophan in the intestinal system is disturbed in IgAN patients, leading to active immune-inflammatory reactions.

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Identification of a novel interplay between intestinal bacteria and metabolites in Chinese patients with IgA nephropathy via integrated microbiome and metabolome approaches

Cited by 17 publications

References 45 publications

The gut microbiome in microscopic polyangiitis with kidney involvement: common and unique alterations, clinical association and values for disease diagnosis and outcome prediction

The gut microbiome in microscopic polyangiitis with kidney involvement: common and unique alterations, clinical association and values for disease diagnosis and outcome prediction

Gut Microbiome Characteristics in IgA Nephropathy: Qualitative and Quantitative Analysis from Observational Studies

Metabolic Dysfunctions of Intestinal Fatty Acids and Tryptophan Reveal Immuno-Inflammatory Response Activation in IgA Nephropathy

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