Alteration of Gut Microbiota Induced by DPP-4i Treatment Improves Glucose Homeostasis

Liao, Xiaoyu; Song, Lingyu; Zeng, Benhua; Qiu, Yuyang; Liu, Bingyao; Qu, Hua; Zheng, Yi; Long, Min; Zhou, Huifang; Wang, Yuan; Du, Yingxuan; Xu, Jing; Shen, Rufei; Tong, Qiang; Cai, Leiqin; Li, Xing; Guo, Shaodong; Yang, Gangyi; Zhu, Zhiming; Pu, Ximing; Wei, Hong; Wang, Cong-Yi

doi:10.2139/ssrn.3284852

Cited by 4 publications

(4 citation statements)

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“…Recent studies have shown that the ability of drugs to modulate the gut microbiota and alleviate disease symptoms could be transferred through fecal transplantation [44][45][46][47]. In our study, microbiota transfer to GF rats showed that colonization of the berberine-altered microbiota could prevent stress-induced visceral hypersensitivity, thus providing evidence for the key role of gut microbiota modulation in the therapeutic action of berberine.…”

Section: Discussionsupporting

confidence: 59%

Berberine alleviates visceral hypersensitivity in rats by altering gut microbiome and suppressing spinal microglial activation

et al. 2021

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Accumulating evidence shows that agents targeting gut dysbiosis are effective for improving symptoms of irritable bowel syndrome (IBS). However, the potential mechanisms remain unclear. In this study we investigated the effects of berberine on the microbiota-gut-brain axis in two rat models of visceral hypersensitivity, i.e., specific pathogen-free SD rats subjected to chronic water avoidance stress (WAS) and treated with berberine (200 mg· kg−1 ·d−1, ig, for 10 days) as well as germ-free (GF) rats subjected to fecal microbiota transplantation (FMT) from a patient with IBS (designated IBS-FMT) and treated with berberine (200 mg· kg−1 ·d−1, ig, for 2 weeks). Before the rats were sacrificed, visceral sensation and depressive behaviors were evaluated. Then colonic tryptase was measured and microglial activation in the dorsal lumbar spinal cord was assessed. The fecal microbiota was profiled using 16S rRNA sequencing, and short chain fatty acids (SCFAs) were measured. We showed that berberine treatment significantly alleviated chronic WAS-induced visceral hypersensitivity and activation of colonic mast cells and microglia in the dorsal lumbar spinal cord. Transfer of fecal samples from berberine-treated stressed donors to GF rats protected against acute WAS. FMT from a patient with IBS induced visceral hypersensitivity and pro-inflammatory phenotype in microglia, while berberine treatment reversed the microglial activation and altered microbial composition and function and SCFA profiles in stools of IBS-FMT rats. We demonstrated that berberine did not directly influence LPS-induced microglial activation in vitro. In both models, several SCFA-producing genera were enriched by berberine treatment, and positively correlated to the morphological parameters of microglia. In conclusion, activation of microglia in the dorsal lumbar spinal cord was involved in the pathogenesis of IBS caused by dysregulation of the microbiota–gut–brain axis, and the berberine-altered gut microbiome mediated the modulatory effects of the agent on microglial activation and visceral hypersensitivity, providing a potential option for the treatment of IBS.

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Section: Discussionsupporting

confidence: 59%

Berberine alleviates visceral hypersensitivity in rats by altering gut microbiome and suppressing spinal microglial activation

et al. 2021

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“…The samples were immediately collected in sterile tubes on ice and stored at -80°C. Fecal genomic DNA extraction, PCR amplification, and sequencing were conducted by Majorbio BioPharm Technology Co., Ltd. (Shanghai, China) [ 23 , 24 ].The procedure of DNA extraction, PCR amplification, and sequencing are (available here ) in the supplementary material.…”

Section: Methodsmentioning

confidence: 99%

Fecal Microbiota Transplantation Is a Promising Method to Restore Gut Microbiota Dysbiosis and Relieve Neurological Deficits after Traumatic Brain Injury

Tang

Zhou

et al. 2021

Oxidative Medicine and Cellular Longevity

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Background. Traumatic brain injury (TBI) can induce persistent fluctuation in the gut microbiota makeup and abundance. The present study is aimed at determining whether fecal microbiota transplantation (FMT) can rescue microbiota changes and ameliorate neurological deficits after TBI in rats. Methods. A controlled cortical impact (CCI) model was used to simulate TBI in male Sprague-Dawley rats, and FMT was performed for 7 consecutive days. 16S ribosomal RNA (rRNA) sequencing of fecal samples was performed to analyze the effects of FMT on gut microbiota. Modified neurological severity score and Morris water maze were used to evaluate neurobehavioral functions. Metabolomics was used to screen differential metabolites from the rat serum and ipsilateral brains. The oxidative stress indices were measured in the brain. Results. TBI induced significance changes in the gut microbiome, including the alpha- and beta-bacterial diversity, as well as the microbiome composition at 8 days after TBI. On the other hand, FMT could rescue these changes and relieve neurological deficits after TBI. Metabolomics results showed that the level of trimethylamine (TMA) in feces and the level of trimethylamine N-oxide (TMAO) in the ipsilateral brain and serum was increased after TBI, while FMT decreased TMA levels in the feces, and TMAO levels in the ipsilateral brain and serum. Antioxidant enzyme methionine sulfoxide reductase A (MsrA) in the ipsilateral hippocampus was decreased after TBI but increased after FMT. In addition, FMT elevated SOD and CAT activities and GSH/GSSG ratio and diminished ROS, GSSG, and MDA levels in the ipsilateral hippocampus after TBI. Conclusions. FMT can restore gut microbiota dysbiosis and relieve neurological deficits possibly through the TMA-TMAO-MsrA signaling pathway after TBI.

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“…The nontarget metabolomic experimental steps were based on a validated method as previously described [18]. The data were analyzed on the free online platform of Majorbio Cloud Platform (https://www.majorbio.com).…”

Section: Nontarget Metabolomic Analysismentioning

confidence: 99%

Self-Control Study on the Impact of Buzhong Yiqi Prescription on the Gut Microbiota of Obese Patients with PCOS and Phlegm-Dampness Syndrome Caused by Spleen Deficiency

Ni¹,

Cheng²,

Ding³

et al. 2020

Preprint

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Background: Gut microbiota disorders have been closely related to polycystic ovarian syndrome (PCOS). Buzhong Yiqi prescription (BZYQ) has a great clinical effect on the treatment of obese patients with PCOS and phlegm-dampness syndrome caused by spleen deficiency (SPSD). This study was performed to explore the alterations in the gut microbiota and fecal metabolites in obese patients with PCOS and SPSD who received BZYQ treatment. Methods: A total of 50 obese patients with PCOS and SPSD were recruited from the Changhai Hospital in Shanghai and accepted three months of BZYQ treatment. Sex hormone were detected and oral glucose tolerance was tested in the outpatient laboratory before and after the BZYQ treatment. Fecal samples were detected by 16S rRNA high-throughput sequencing and nontargeted metabolomic methods to determine the structure of the gut microbiota and metabolites, respectively.Results: BZYQ could significantly alleviate the serum DHEAS (p<0.001) and T level (p<0.001) in obese patients with PCOS and SPSD. The structure of the gut microbiota changed significantly after the BZYQ treatment. In particular, at the phylum level, the abundance of Spirochaetae was significantly higher after treatment than that before treatment. At the genus level, the abundances of [Eubacterium]_rectale_group, Escherichia-Shigella, and Fusicatenibacter were significantly higher after treatment than those before treatment, but the abundance of Megamonas was significantly lower. A total of 106 differential metabolites and 14 KEGG enrichment pathways were quantified. The disorder in the gut microbiota and fecal metabolites of obese patients with PCOS and SPSD were closely related to hyperandrogenemia and insulin resistance. The level of tetracosanoic acid was negatively correlated with serum DHEA level (p<0.05), while the palmitoleic acid level was negatively correlated with serum T level (p<0.05). Conclusions: BZYQ could ameliorate the serum androgen level and had an impact on the gut microbiota and metabolites in obese patients with PCOS and SPSD.Trial registration: Chinese Clinical Trial Registry, ChiCTR-IPR-16009166. Registered 26 September 2016, http://www.chictr.org.cn/showproj.aspx?proj=14956

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Alteration of Gut Microbiota Induced by DPP-4i Treatment Improves Glucose Homeostasis

Cited by 4 publications

References 0 publications

Berberine alleviates visceral hypersensitivity in rats by altering gut microbiome and suppressing spinal microglial activation

Berberine alleviates visceral hypersensitivity in rats by altering gut microbiome and suppressing spinal microglial activation

Fecal Microbiota Transplantation Is a Promising Method to Restore Gut Microbiota Dysbiosis and Relieve Neurological Deficits after Traumatic Brain Injury

Self-Control Study on the Impact of Buzhong Yiqi Prescription on the Gut Microbiota of Obese Patients with PCOS and Phlegm-Dampness Syndrome Caused by Spleen Deficiency

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