Integrative Analysis of Gut Microbiota and Fecal Metabolites in Rats after Prednisone Treatment

Zhang, Jing; Feng, Dan; Law, Helen Ka-wai; Wu, Ying; Zhu, Geng; Huang, Wenyan; Kang, Youjeong

doi:10.1128/spectrum.00650-21

Cited by 22 publications

(29 citation statements)

References 46 publications

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“…A recent study revealed that longterm prednisone treatment affects gut microbiota composition and fecal metabolites in mouse models. For instance, in rats treated with 6-week prednisone, the relative abundances of the genera Eisenbergiella and Alistipes decreased, whereas that of Anaerobacterium increased significantly (7). Tourret et al found decreased Bacteroidetes and increased Firmicutes levels in mouse feces after 14 days of prednisone treatment (8).…”

Section: Introductionmentioning

confidence: 99%

Dysbiosis of gut microbiota and decreased propionic acid associated with metabolic abnormality in Cushing’s syndrome

Zhang

Deng

et al. 2023

Front. Endocrinol.

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ObjectiveChronic hypercortisolism leads to a phenotype resembling metabolic syndrome. We aimed to investigate the association between gut microbiota and metabolic abnormalities in endogenous hypercortisolism (Cushing’s syndrome).MethodsA total of 23 patients with Cushing’s syndrome (18 female and 5 men, aged 47.24 ± 12.99 years) and 30 age-, sex-and BMI-matched healthy controls (18 female and 12 men, aged 45.03 ± 6.69 years) were consecutively recruited. Differences in gut microbiota and plasma short-chain fatty acid (SCFAs) concentrations between the Cushing’s syndrome patients and controls were analyzed by 16S rRNA sequencing and gas chromatography-mass spectrometry (GC-MS).ResultsCompared to the controls, the Simpson and Pielou indices of α diversity were dramatically decreased in Cushing’s syndrome (P < 0.05). The gut microbiota community structure differed significantly between Cushing’s syndrome patients and controls. Compared to controls, the bacterial communities of the Cushing’s syndrome patients were enriched in Proteobacteria and Escherichia-Shigella, and depleted in Firmicutes, including Agathobacter, Blautia, Anaerostipes, Eubacterium_eligens_group, and Lachnospira. Spearman analysis demonstrated that HbA1c, SBP, DBP, and cortisol levels were significantly positively correlated with Proteobacteria and Escherichia-Shigella, whereas negatively correlated with Agathobacter, Blautia, Anaerostipes, Eubacterium_hallii_group, and Lachnospira, etc. Cushing’s syndrome patients also had a lower propionic acid concentration (0.151±0.054 vs. 0.205±0.032 µg/mL, P=0.039) than controls. Furthermore, the level of propionic acid was negatively correlated with systolic pressure and cortisol levels (P<0.05).ConclusionGut microbiota dysbiosis and decreased propionic acid levels were observed in patients with Cushing’s, suggesting that the gut microbiota may be a potential therapeutic intervention target to improve hypercortisolism-related metabolic abnormalities.

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Section: Introductionmentioning

confidence: 99%

Dysbiosis of gut microbiota and decreased propionic acid associated with metabolic abnormality in Cushing’s syndrome

Zhang

Deng

et al. 2023

Front. Endocrinol.

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“…Our findings indicate a noticeable change in microbial signature, with the strongest alteration experienced in Eggerthellas; specifically, E. lentha, and no taxa associated with short PFS show significantly increased abundance in the AB-treated group. So far, only preclinical studies have reported the shift in the intestinal microbiome due to systemic corticosteroid treatment [27,36]. We found only a minor bacterial conversion in steroid-treated patients with an increased abundance of Proteobacteria, including Escherichia and E.coli.…”

Section: Discussionmentioning

confidence: 55%

Non-Small Cell Lung Cancer Patients Treated with Anti-PD1 Immunotherapy Show Distinct Microbial Signatures and Metabolic Pathways According to Clinical Outcomes

Dóra

Ligeti

Kovács

et al. 2022

Preprint

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Background: Clinical outcomes of immune checkpoint inhibitor (ICI)-treated non-small cell lung cancer (NSCLC) patients might be associated with the gut metagenome. Methods: Sixty-two Caucasian advanced-stage NSCLC patients treated with anti-PD1 immunotherapy were included. Gut bacterial signatures were evaluated by metagenomic sequencing and correlated with progression-free survival (PFS), PD-L1 expression defined by immunohistochemistry, and other clinicopathological parameters. The predictive role of PFS-related key bacteria was confirmed with multivariate statistical models and validated on an additional patient cohort (n=60). The functional microbial signature of distinct patient groups were determined by analyzing metabolic pathways. A random forest (RF) machine learning algorithm was used to assess the predictive power of taxonomic and metabolic microbial signatures. Results: Alpha-diversity showed no significant difference in any comparison. However, there was a significant difference in beta-diversity between patients with long- (>6 months) vs. short (≤6 months) PFS and between chemotherapy (CHT)-treated vs. CHT-naive cases. Short PFS was associated with increased abundance of Firmicutes (F) and Actinobacteria phyla, whereas elevated abundance of Euryarcheota was specific for low-PD-L1 expression. F/Bacteroides (F/B) ratio was significantly increased in patients with short PFS. Multivariate analysis revealed an association between Alistipes shahii, Alistipes finegoldii, Barnesiella visceriola, and long PFS. In contrast, Streptococcus salivarius, Streptococcus vestibularis, and Bifidobacterium breve were associated with short PFS. Taxonomic profiles performed superiorly in predicting PFS (AUC=0.74), while metabolic pathways including Amino Acid Synthesis and Fermentation were better predictors of PD-L1 expression (AUC=0.87). Conclusion: The specific metagenomic features of the gut microbiome including bacterial taxonomy and metabolic pathways are suggestive of ICI efficacy and PD-L1 expression in NSCLC patients.

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“…Eisenbergiella has also been found enriched in individuals with neuropsychiatric disorders, such as ASD, depression, and Parkinson’s disease 50–52 , in chickens and mice infected with pathogens 53, 54 , and in children with an allergy to cow’s milk 55 . It was found reduced in rats after immunosuppressive/anti-inflammatory treatment 56 , suggesting general associations with pro-inflammatory processes and immune activation. Higher abundance of Eisenbergiella has also been linked to a high energy diet (rich in carbohydrates, fat, and protein) 57 and to metabolic disorders, such as gestational diabetes mellitus 58 .…”

Section: Discussionmentioning

confidence: 92%

The gut-microbiome in adult Attention-deficit/hyperactivity disorder - A Meta-analysis

Jakobi,

Vlaming,

Mulder

et al. 2023

Preprint

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Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental condition that persists into adulthood in the majority of individuals. While the gut-microbiome seems to be relevant for ADHD, the few publications on gut-microbial alterations in ADHD are inconsistent, in the investigated phenotypes, sequencing method/region, preprocessing, statistical approaches, and findings. To identify gut-microbiome alterations in adult ADHD, robust across studies and statistical approaches, we harmonized bioinformatic pipelines and analyses of raw 16S rRNA sequencing data from four adult ADHD case-control studies (NADHD=312, NNoADHD=305). We investigated diversity and differential abundance of selected genera (logistic regression and ANOVA-like Differential Expression tool), corrected for age and sex, and meta-analyzed the study results. Converging results were investigated for association with hyperactive/impulsive and inattentive symptoms across all participants. Beta diversity was associated with ADHD diagnosis but showed significant heterogeneity between cohorts, despite harmonized analyses. Several genera were robustly associated with adult ADHD; e.g.,Ruminococcus_torques_group(LogOdds=0.17, pfdr=4.42×10−2), which was more abundant in adults with ADHD, andEubacterium_xylanophilum_group(LogOdds= −0.12,pfdr=6.9 x 10−3), which was less abundant in ADHD.Ruminococcus_torques_groupwas further associated with hyperactivity/impulsivity symptoms andEisenbergiellawith inattention and hyperactivity/impulsivity (pfdr<0.05). The literature points towards a role of these genera in inflammatory processes. Irreproducible results in the field of gut-microbiota research, due to between study heterogeneity and small sample sizes, stress the need for meta-analytic approaches and large sample sizes. While we robustly identified genera associated with adult ADHD, that might overall be considered beneficial or risk-conferring, functional studies are needed to shed light on these properties.

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Integrative Analysis of Gut Microbiota and Fecal Metabolites in Rats after Prednisone Treatment

Abstract: Prednisone is widely used in chronic glomerular diseases, immunological disorders, and rheumatic diseases for its anti-inflammatory and immunosuppressive properties. It is a synthetic glucocorticoid (GC) that shows therapeutic effects after conversion to prednisolone by the liver.

Cited by 22 publications

References 46 publications

Dysbiosis of gut microbiota and decreased propionic acid associated with metabolic abnormality in Cushing’s syndrome

Dysbiosis of gut microbiota and decreased propionic acid associated with metabolic abnormality in Cushing’s syndrome

Non-Small Cell Lung Cancer Patients Treated with Anti-PD1 Immunotherapy Show Distinct Microbial Signatures and Metabolic Pathways According to Clinical Outcomes

The gut-microbiome in adult Attention-deficit/hyperactivity disorder - A Meta-analysis

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