Commensal microbiota-induced microRNA modulates intestinal epithelial permeability through the small GTPase ARF4

Nakata, Kazuaki; Sugi, Yutaka; Narabayashi, Hikari; Kobayakawa, Tetsuro; Nakanishi, Yusuke; Tsuda, Masato; Hosono, Akira; Kaminogawa, Shuichi; Hanazawa, Shigemasa; Takahashi, Kyôko

doi:10.1074/jbc.m117.788596

Cited by 103 publications

(79 citation statements)

References 33 publications

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“…Other studies have examined intestinal epithelial cells directly to ensure that the observed miRNA differences were caused by the effect of gut microbes on epithelial cells alone. Using microarray and qPCR data, Nakata and colleagues [112] showed that miR-21-5p is expressed at higher levels in the small and large intestines of conventional mice than in germ-free mice. They then went on to show that exposing HT-29 and SW480 cells (two CRC cell lines) to heat-killed Bacteroides acidifaciens type A43 and to Lactobacillus johnsonii 129 resulted in an upregulation of miR-21-5p, suggesting that molecules derived from these bacteria (and not live bacteria alone) can directly regulate the expression of this well-studied oncomiRNA [112].…”

Section: The Gut Microbiome and Non-coding Rnasmentioning

confidence: 99%

“…Using microarray and qPCR data, Nakata and colleagues [112] showed that miR-21-5p is expressed at higher levels in the small and large intestines of conventional mice than in germ-free mice. They then went on to show that exposing HT-29 and SW480 cells (two CRC cell lines) to heat-killed Bacteroides acidifaciens type A43 and to Lactobacillus johnsonii 129 resulted in an upregulation of miR-21-5p, suggesting that molecules derived from these bacteria (and not live bacteria alone) can directly regulate the expression of this well-studied oncomiRNA [112]. Paradoxically, both of these bacteria are regarded as probiotic bacteria and not oncogenic [113,114], again indicating the need for studies focused on functional outcomes.…”

Section: The Gut Microbiome and Non-coding Rnasmentioning

confidence: 99%

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Impact of the gut microbiome on the genome and epigenome of colon epithelial cells: contributions to colorectal cancer development

2019

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In recent years, the number of studies investigating the impact of the gut microbiome in colorectal cancer (CRC) has risen sharply. As a result, we now know that various microbes (and microbial communities) are found more frequently in the stool and mucosa of individuals with CRC than healthy controls, including in the primary tumors themselves, and even in distant metastases. We also know that these microbes induce tumors in various mouse models, but we know little about how they impact colon epithelial cells (CECs) directly, or about how these interactions might lead to modifications at the genetic and epigenetic levels that trigger and propagate tumor growth. Rates of CRC are increasing in younger individuals, and CRC remains the second most frequent cause of cancer-related deaths globally. Hence, a more in-depth understanding of the role that gut microbes play in CRC is needed. Here, we review recent advances in understanding the impact of gut microbes on the genome and epigenome of CECs, as it relates to CRC. Overall, numerous studies in the past few years have definitively shown that gut microbes exert distinct impacts on DNA damage, DNA methylation, chromatin structure and non-coding RNA expression in CECs. Some of the genes and pathways that are altered by gut microbes relate to CRC development, particularly those involved in cell proliferation and WNT signaling. We need to implement more standardized analysis strategies, collate data from multiple studies, and utilize CRC mouse models to better assess these effects, understand their functional relevance, and leverage this information to improve patient care.

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Section: The Gut Microbiome and Non-coding Rnasmentioning

confidence: 99%

Section: The Gut Microbiome and Non-coding Rnasmentioning

confidence: 99%

Impact of the gut microbiome on the genome and epigenome of colon epithelial cells: contributions to colorectal cancer development

2019

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“…However, we could not nd in the literature evidences of association between this miRNA and gut microbiota. implications in the regulation of intestinal epithelial permeability (Nakata et al, 2017). Otherwise, miR-130b-3p was only correlated with B. eggerthi abundance and there is evidence that the expression of this miRNA was in uenced by microbial status in intestinal epithelial stem cell of conventionalized mice compared to germ-free mice (Peck et al, 2017), showing that the miRNAs expression could be modulated by gut microbiota.…”

Section: Discussionmentioning

confidence: 99%

“…Additionally, the gut microbiota regulates miRNA expression in IECs subtypes, and this regulation may alter intestinal homeostasis (Nakata et al, 2017). In this sense, it was demonstrated that the expression of some miRNAs is different among IEC subtypes and the difference depends on microbial patterns (Peck et al, 2017).…”

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confidence: 99%

Novel Interactions Between Circulating microRNAs and Gut Microbiota Composition in Human Obesity.

Assmann

Cuevas-Sierra

Riezu‐Boj

et al. 2020

Preprint

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Background: Unbalances in microRNAs (miRNA) and gut microbiota patterns have been proposed as putative factors concerning onset and development of obesity and other metabolic diseases. However, the determinants that mediate the interactions between miRNAs and the gut microbiome impacting on obesity are scarcely understood. Thus, the aim of this article was to investigate possible interactions between circulating miRNAs and gut microbiota composition in obesity. Method: The analyzed sample comprised 78 subjects with obesity [cases, body mass index (BMI): 30 – 40 kg/m2] and 25 eutrophic individuals (controls, BMI £ 25 kg/m2). The expression of 96 miRNAs was investigated in plasma of all individuals using miRCURY LNA miRNA Custom PCR Panels (Exiqon). Bacterial DNA sequencing was performed following the Illumina 16S protocol. The FDR (Benjamini-Hochberg test, q-value) correction was used for multiple comparison analyses.Results: A total of 26 circulating miRNAs and 12 bacterial species were found differentially expressed between cases and controls. Interestingly, an interaction among three miRNAs (miR-130b-3p, miR-185-5p, and miR-21-5p) with Bacteroides eggerthi, and BMI levels was evidenced (r2= 0.148, P= 0.004). Those miRNAs that correlated with obesity-associated gut bacteria abundance are known to regulate target genes that participate in metabolism-related pathways, such as fatty acid degradation, carbohydrate digestion and absorption, insulin signaling, and glycerolipid metabolism. Conclusion: This study characterized an interaction between the abundance of 4 bacterial species and 14 circulating miRNAs in relation to body adiposity. Moreover, the current study also suggests that miRNAs may serve as a communication mechanism between the gut microbiome and human hosts. Clinical trial registration: clinicaltrials.gov (reg. no. NCT02737267).

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“…Wild-type (WT) and MyD88 2/2 BALB/c mice were purchased from CLEA Japan (Tokyo, Japan) and Oriental BioService (Kyoto, Japan), respectively. Mice were bred under conventional (CV) or germ-free (GF) conditions as described previously (24). Female mice were used at 9-13 wk of age.…”

Section: Micementioning

confidence: 99%

Regulation of Gene Expression through Gut Microbiota-Dependent DNA Methylation in Colonic Epithelial Cells

et al. 2020

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A huge number of commensal bacteria inhabit the intestine, which is equipped with the largest immune system in the body. Recently, the regulation of various physiological functions of the host by these bacteria has attracted attention. In this study, the effects of commensal bacteria on gene expression in colonic epithelial cells (CoECs) were investigated with focus on regulation of DNA methylation. RNA sequencing analyses of CoECs from conventional, germ-free, and MyD88 2/2 mice indicated that, out of the genes affected by commensal bacteria, those downregulated in a MyD88-independent manner were most frequently observed. Furthermore, when the 59 regions of genes downregulated by commensal bacteria in CoECs were captured using a customized array and immunoprecipitated with the anti-methyl cytosine Ab, a certain population of these genes was found to be highly methylated. Comprehensive analysis of DNA methylation in the 59 regions of genes in CoECs from conventional and germ-free mice upon pulldown assay with methyl-CpG-binding domain protein 2 directly demonstrated that DNA methylation in these regions was influenced by commensal bacteria. Actually, commensal bacteria were shown to control expression of Aldh1a1, which encodes a retinoic acid-producing enzyme and plays an important role in the maintenance of intestinal homeostasis via DNA methylation in the overlapping 59 region of Tmem267 and 3110070M22Rik genes in CoECs. Collectively, it can be concluded that regulation of DNA methylation in the 59 regions of a specific population of genes in CoECs acts as a mechanism by which commensal bacteria have physiological effects on the host.

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Commensal microbiota-induced microRNA modulates intestinal epithelial permeability through the small GTPase ARF4

Cited by 103 publications

References 33 publications

Impact of the gut microbiome on the genome and epigenome of colon epithelial cells: contributions to colorectal cancer development

Impact of the gut microbiome on the genome and epigenome of colon epithelial cells: contributions to colorectal cancer development

Novel Interactions Between Circulating microRNAs and Gut Microbiota Composition in Human Obesity.

Regulation of Gene Expression through Gut Microbiota-Dependent DNA Methylation in Colonic Epithelial Cells

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