Altered gut microbiome promotes proteinuria in mice induced by Adriamycin

Jiang, Qian; He, Xiwei; Zou, Yuntao; Ding, Yin; Huang, Li

doi:10.1186/s13568-018-0558-7

Cited by 25 publications

(14 citation statements)

References 31 publications

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“…Turicibacter spp. has anti-inflammatory properties 66 and its decreased abundance has been reported in BALB/C mice with adriamycin-induced nephropathy 40 and in 5/6 nephrectomized rats 39 , which is consistent with our current study. Dysregulation of Turicibacter was found in adenine-induced CKD rats and was reversed with high-fiber diets 67 .…”

Section: Discussionsupporting

confidence: 93%

“…valericigenes could produce valerate as its major product 77 . The increased abundance of the Oscillibacter genus has been reported in adriamycin-induced BALB/C mice 40 and patients with stroke and transient ischemic attack 78 . Although the Blautia genus was increased significantly in our UUO rats, its relative abundance was low in both groups (0.019% and 0.074% in the sham and UUO rats, respectively).…”

Section: Discussionmentioning

confidence: 92%

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Unilateral ureteral obstruction causes gut microbial dysbiosis and metabolome disorders contributing to tubulointerstitial fibrosis

Chen

Liu

et al. 2019

Exp Mol Med

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Chronic kidney disease (CKD) increases the risk and prevalence of cardiovascular disease (CVD) morbidity and mortality. Recent studies have revealed marked changes in the composition of the microbiome and the metabolome and their potential influence in renal disease and CVD via the accumulation of microbial-derived uremic toxins. However, the effect of unilateral ureteral obstruction (UUO) on the gut microbiome and circulating metabolites is unknown. Male Sprague-Dawley rats were randomized to UUO and sham-operated control groups. Renal histology, colonic microbiota, and plasma metabolites were examined two weeks later. We employed 16S rRNA sequence and untargeted metabolomic analyses to explore the changes in colonic microbiota and plasma metabolites and their relationship with tubulointerstitial fibrosis (TIF). The UUO rats exhibited tubular atrophy and dilatation, interstitial fibrosis and inflammatory cell infiltration in the obstructed kidney. UUO rats showed significant colonic enrichment and depletion of genera. Significant differences were identified in 219 plasma metabolites involved in lipid, amino acid, and bile acid metabolism, which were consistent with gut microbiota-related metabolism. Interestingly, tryptophan and its metabolites kynurenine, 5-hydroxytryptophan and 5-hydroxytryptamine levels, which were linked with TIF, correlated with nine specific genera. Plasma tryptophan level was positively correlated with Clostridium IV, Turicibacter, Pseudomonas and Lactobacillales, and negatively correlated with Oscillibacter, Blautia, and Intestinimonas, which possess the genes encoding tryptophan synthase (K16187), indoleamine 2,3-dioxygenase (K00463) and tryptophan 2,3-dioxygenase (K00453) and their corresponding enzymes (EC:1.13.11.52 and EC:1.13.11.11) that exacerbate TIF. In conclusion, UUO results in profound changes in the gut microbiome and circulating metabolites, events that contribute to the pathogenesis of inflammation and TIF.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 92%

Unilateral ureteral obstruction causes gut microbial dysbiosis and metabolome disorders contributing to tubulointerstitial fibrosis

Chen

Liu

et al. 2019

Exp Mol Med

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“…Further experiments will be carried out to elucidate the underlying mechanism. Previous study showed that treatment of BALB/C mice with DOX at a dose of 10 mg/kg for 2 weeks altered the stool microbiome characterized by the increased Odoribacter and decreased Turicibacter , Marvinbryantia , and Rikenella (Jiang et al, 2018). The discrepancy may be due to differences in dose and processing time of DOX and strains of mice.…”

Section: Discussionmentioning

confidence: 99%

Glabridin Prevents Doxorubicin-Induced Cardiotoxicity Through Gut Microbiota Modulation and Colonic Macrophage Polarization in Mice

et al. 2019

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The chemotherapeutic drug doxorubicin (DOX) provokes a dose-related cardiotoxicity. Thus, there is an urgent need to identify the underlying mechanisms and develop strategies to overcome them. Here we demonstrated that glabridin (GLA), an isoflavone from licorice root, prevents DOX-induced cardiotoxicity through gut microbiota modulation and colonic macrophage polarization in mice. GLA reduced DOX-induced leakage of myocardial enzymes including aminotransferase, creatine kinase, lactate dehydrogenase, and creatine kinase-MB. GLA downregulated pro-apoptotic proteins (Bax, cleaved-caspase 9 and cleaved-caspase 3) and upregulated anti-apoptotic proteins (HAX-1 and Bcl-2) in the cardiac tissues. In addition, GLA modulated DOX-induced dysbiosis of gut microbiota and thereby decreased the ratio of M1/M2 colonic macrophage, accompanied by the downregulated lipopolysaccharide (LPS) and upregulated butyrate in the feces and peripheral blood. The leakage of myocardial enzymes induced by the DOX was decreased by antibiotics treatment, but not altered by co-treatment with the GLA and antibiotics. The ratio of M1/M2 colonic macrophage and leakage of myocardial enzymes reduced by the GLA were greatly increased by the Desulfovibrio vulgaris or LPS but decreased by the butyrate. Depletion of the macrophage attenuated DOX-induced cardiotoxicity but failed to further affect the effects of GLA. Importantly, GLA decreased production of M1 cytokines (IL-1β and TNF-α) but increased production of M2 cytokines (IL-10 and TGF-β) in the colonic macrophage with the downregulation of NF-κB and the upregulation of STAT6. In summary, GLA prevents DOX-induced cardiotoxicity through gut microbiota modulation and colonic macrophage polarization, and may serve as a potential therapeutic strategy for the DOX-induced cardiotoxicity.

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“…Changes in these “butyrogenic” bacteria [44] may in turn influence metabolic, inflammatory bowel disorders. Indeed, butyrate, which can be used as a source of energy by the host, confers many benefits including anti-inflammatory effects [45]. Likewise, Phascolarctobacterium enriched in REE-L+ is a Gram-negative genus able to produce SCFAs.…”

Section: Discussionmentioning

confidence: 99%

Effects of Maternal Supplementation with Rare Earth Elements during Late Gestation and Lactation on Performances, Health, and Fecal Microbiota of the Sows and Their Offspring

Xiong

Pang

et al. 2019

Animals

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Simple SummaryThe immunological and metabolic status of breeding sows directly affect the overall productivity of porcine operations. Especially, maternal health status during the transition from gestation to lactation are important in maintaining health and growth of the suckling piglets. Rare earth elements (REEs) have been considered as a promising natural feed additive and been reported to exert their activity locally within the gastrointestinal tract, including effects on the bacterial microflora and on nutrient utilization. The present study was conducted to explore the effects of dietary maternal REE supplementation during late gestation and lactation on sows and their offspring. After the experiment, we found that maternal REE addition enhanced antioxidant activity and immunity of sows and their suckling piglets. At the same time, REE supplementation during perinatal period improved the reproductivity of the sows as well as the growth of their offspring. Besides, maternal REEs supply altered the intestinal microbiota community and composition of sows as well as their offspring, and Spearman correlation analysis shows that fecal bacteria are associated with the antioxidase, inflammatory factors of the sows and offspring as well as average daily gain of the suckling piglets. In addition, our results suggested that REE supplementation during both gestation and lactation are more beneficial to sows and their offspring than supplementation during only late gestation. This paper holds promise in providing efficient feeding strategies in swine production.AbstractThe study was conducted to investigate the effects of maternal supplementation with rare earth elements (REEs) on sows and their offspring. During late gestation, 120 multiparous sows were divided randomly into the control group (Basal diet) and REE-G group (Basal diet supplemented with 200 mg REE/kg). After delivery, REE-G group was further divided into two groups: REE-L- (Change to basal diet during lactation) and REE-L+ group (REE diet all the time). Our results showed that maternal REE supplementation improved the antioxidant and immunity of sows and piglets. Additionally, REE supply during late gestation significantly decreased the coefficient of within-litter variation (CV) in birth weight and increased the weaning weights and the average daily gain (ADG) of piglets. During lactation, the insulin-like growth factor-1 (IGF-1) levels in piglets of REE-L+ group were higher, while no difference between REE-L- and the control group. More beneficial bacteria (Christensenellaceae and Ruminococcaceae) were found in the REE-L+ group while some opportunistic pathogens (Proteobacteria and Campylobacter) were relatively suppressed. Fecal microbiota showed correlation with antioxidase, inflammatory factors, and average daily gain (ADG). Collectively, our findings indicated that REEs added in both gestation and lactation was more conducive to establish a healthier status for sows and their offspring.

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Altered gut microbiome promotes proteinuria in mice induced by Adriamycin

Cited by 25 publications

References 31 publications

Unilateral ureteral obstruction causes gut microbial dysbiosis and metabolome disorders contributing to tubulointerstitial fibrosis

Unilateral ureteral obstruction causes gut microbial dysbiosis and metabolome disorders contributing to tubulointerstitial fibrosis

Glabridin Prevents Doxorubicin-Induced Cardiotoxicity Through Gut Microbiota Modulation and Colonic Macrophage Polarization in Mice

Effects of Maternal Supplementation with Rare Earth Elements during Late Gestation and Lactation on Performances, Health, and Fecal Microbiota of the Sows and Their Offspring

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