Integrated Analysis of Transcriptome mRNA and miRNA Profiles Reveals Self-Protective Mechanism of Bovine MECs Induced by LPS

Chen, Ling; Liu, Xiaolin; Li, Zhixiong; Wang, Jian; Tian, Rongfu; Zhang, Huilin

doi:10.3389/fvets.2022.890043

Cited by 7 publications

(8 citation statements)

References 77 publications

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“…Indeed, the current study identifies bacterial pathogens (i.e., Staphylococcus ), and inflammatory miRNAs (i.e., let-7a-5p) which are elevated in the milk of mothers with colicky infants. This finding is consistent with a study of bacterial lipopolysaccharide-mediated mastitis in mammary epithelial cells, which reported perturbations in both let-7a-5p and milk cytokines in response to bacterial antigens [ 55 ]. Transfer of these inflammatory components to the infant gut may contribute to an inflammatory state and produce the characteristic symptoms of infant colic ( Figure 6 ).…”

Section: Discussionsupporting

confidence: 92%

The Association between Infant Colic and the Multi-Omic Composition of Human Milk

et al. 2023

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Infant colic is a common condition with unclear biologic underpinnings and limited treatment options. We hypothesized that complex molecular networks within human milk (i.e., microbes, micro-ribonucleic acids (miRNAs), cytokines) would contribute to colic risk, while controlling for medical, social, and nutritional variables. This hypothesis was tested in a cohort of 182 breastfed infants, assessed with a modified Infant Colic Scale at 1 month. RNA sequencing was used to interrogate microbial and miRNA features. Luminex assays were used to measure growth factors and cytokines. Milk from mothers of infants with colic (n = 28) displayed higher levels of Staphylococcus (adj. p = 0.038, d = 0.30), miR-224-3p (adj. p = 0.023, d = 0.33), miR-125b-5p (adj. p = 0.028, d = 0.29), let-7a-5p (adj. p = 0.028, d = 0.27), and miR-205-5p (adj. p = 0.029, d = 0.26) compared to milk from non-colic mother–infant dyads (n = 154). Colic symptom severity was directly associated with milk hepatocyte growth factor levels (R = 0.21, p = 0.025). A regression model involving let-7a-5p, miR-29a-3p, and Lactobacillus accurately modeled colic risk (X2 = 16.7, p = 0.001). Molecular factors within human milk may impact colic risk, and provide support for a dysbiotic/inflammatory model of colic pathophysiology.

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Section: Discussionsupporting

confidence: 92%

The Association between Infant Colic and the Multi-Omic Composition of Human Milk

et al. 2023

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“…We provide deeper insights into the multi-level signatures simultaneously involved in the regulation of mammary gland response to subclinical mastitis. Our data is consistent with previous studies about bovine mastitis that focused on the integration of two omics data sets [26][27][28][29][30][31]48] and at the same time provided deeper insights into the molecular signatures of subclinical mastitis.…”

Section: Discussionsupporting

confidence: 91%

“…However, it is important to note that the application of multi-omics approaches in studying bovine mastitis is still in its early stages. For instance, a few studies integrated two omics data, such as GWAS and RNA-sequencing data [26], transcriptome and miRNA pro les [27,28], or transcriptome and methylome [29][30][31], and revealed novel insights into the genetic and epigenetic basis of mastitis. This highlights the importance of using multiomics approaches to gain a deeper understanding of mastitis and emphasizes the advantage of integrating more omics data for a more comprehensive investigation of the pathogenesis and regulatory mechanisms of mastitis.…”

Section: Resultsmentioning

confidence: 99%

Multi-omics integration identifies regulatory factors underlying bovine subclinical mastitis

WANG,

yang,

Laterrière

et al. 2023

Preprint

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Background Mastitis caused by multiple factors remains one of the most common and costly disease of the dairy industry. Multi-omics approaches enable the comprehensive investigation of the complex interactions between multiple layers of information to provide a more holistic view of disease pathogenesis. Therefore, this study investigated the genomic and epigenomic signatures and the possible regulatory mechanisms underlying subclinical mastitis by integrating RNA sequencing data (mRNA and lncRNA), small RNA sequencing data (miRNA) and DNA methylation sequencing data of milk somatic cells from ten healthy cows and twenty cows with naturally occurring subclinical mastitis caused by Staphylococcus aureus or Staphylococcus chromogenes. Results Functional investigation of the data sets through gene sets analysis uncovered 3458 biological process GO terms and 170 KEGG pathways with altered activities during subclinical mastitis, providing further insights into subclinical mastitis and revealing the involvement of multi-omics signatures in the altered immune responses and impaired mammary gland productivity during subclinical mastitis. The abundant genomic and epigenomic signatures with significant alterations related to subclinical mastitis were observed, including 30,846, 2552, 1276 and 57 differential MHBs (dMHBs), differentially expressed genes (DEGs), lncRNAs (DELs) and miRNAs (DEMs), respectively. Next, five Factors presenting the principal variation of differential multi-omics signatures were identified. The important roles of Factors 1 and Factor 2 in the regulation of immune defense and impaired mammary gland functions during subclinical mastitis were revealed. Also, networks of important functional gene sets with the involvement of multi-OMICs signatures were demonstrated, which contributed to a comprehensive view of the possible regulatory mechanisms underlying subclinical mastitis. Furthermore, multi-omics integration enabled the association of the epigenomic regulatory factors of altered genes in important pathways, such as ‘Staphylococcus aureus infection pathway’ and ‘natural killer cell mediated cytotoxicity pathway’, etc., which provides further insights into mastitis regulatory mechanisms. Moreover, few multi-omics signatures (14 dMHBs, 25 DEGs, 18 DELs and 5 DEMs) were identified as candidate discriminant signatures with capacity of distinguishing subclinical mastitis cows from healthy cows. Conclusion The integration of genomic and epigenomic data by multi-omics approaches in this study provided a better understanding of the molecular mechanisms underlying subclinical mastitis and identified multi-omics candidate discriminant signatures for subclinical mastitis, which may ultimately lead to the development of more effective mastitis control and management strategies.

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“…However, it is important to note that the application of multi-omics approaches in studying bovine mastitis is still in its early stages. For instance, a few studies integrated two omics data, such as GWAS and RNA-sequencing data [ 26 ], transcriptome and miRNA profiles [ 27 – 29 ], or transcriptome and methylome [ 30 – 33 ], and revealed novel insights into the genetic and epigenetic basis of mastitis. This highlights the importance of using multi-omics approaches to gain a deeper understanding of mastitis and emphasizes the advantage of integrating more omics data for a more comprehensive investigation of the pathogenesis and regulatory mechanisms of mastitis.…”

Section: Introductionmentioning

confidence: 99%

Multi-omics integration identifies regulatory factors underlying bovine subclinical mastitis

Wang,

Yang,

Laterrière

et al. 2024

J Animal Sci Biotechnol

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Background Mastitis caused by multiple factors remains one of the most common and costly disease of the dairy industry. Multi-omics approaches enable the comprehensive investigation of the complex interactions between multiple layers of information to provide a more holistic view of disease pathogenesis. Therefore, this study investigated the genomic and epigenomic signatures and the possible regulatory mechanisms underlying subclinical mastitis by integrating RNA sequencing data (mRNA and lncRNA), small RNA sequencing data (miRNA) and DNA methylation sequencing data of milk somatic cells from 10 healthy cows and 20 cows with naturally occurring subclinical mastitis caused by Staphylococcus aureus or Staphylococcus chromogenes. Results Functional investigation of the data sets through gene set analysis uncovered 3458 biological process GO terms and 170 KEGG pathways with altered activities during subclinical mastitis, provided further insights into subclinical mastitis and revealed the involvement of multi-omics signatures in the altered immune responses and impaired mammary gland productivity during subclinical mastitis. The abundant genomic and epigenomic signatures with significant alterations related to subclinical mastitis were observed, including 30,846, 2552, 1276 and 57 differential methylation haplotype blocks (dMHBs), differentially expressed genes (DEGs), lncRNAs (DELs) and miRNAs (DEMs), respectively. Next, 5 factors presenting the principal variation of differential multi-omics signatures were identified. The important roles of Factor 1 (DEG, DEM and DEL) and Factor 2 (dMHB and DEM), in the regulation of immune defense and impaired mammary gland functions during subclinical mastitis were revealed. Each of the omics within Factors 1 and 2 explained about 20% of the source of variation in subclinical mastitis. Also, networks of important functional gene sets with the involvement of multi-omics signatures were demonstrated, which contributed to a comprehensive view of the possible regulatory mechanisms underlying subclinical mastitis. Furthermore, multi-omics integration enabled the association of the epigenomic regulatory factors (dMHBs, DELs and DEMs) of altered genes in important pathways, such as ‘Staphylococcus aureus infection pathway’ and ‘natural killer cell mediated cytotoxicity pathway’, etc., which provides further insights into mastitis regulatory mechanisms. Moreover, few multi-omics signatures (14 dMHBs, 25 DEGs, 18 DELs and 5 DEMs) were identified as candidate discriminant signatures with capacity of distinguishing subclinical mastitis cows from healthy cows. Conclusion The integration of genomic and epigenomic data by multi-omics approaches in this study provided a better understanding of the molecular mechanisms underlying subclinical mastitis and identified multi-omics candidate discriminant signatures for subclinical mastitis, which may ultimately lead to the development of more effective mastitis control and management strategies.

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Integrated Analysis of Transcriptome mRNA and miRNA Profiles Reveals Self-Protective Mechanism of Bovine MECs Induced by LPS

Cited by 7 publications

References 77 publications

The Association between Infant Colic and the Multi-Omic Composition of Human Milk

The Association between Infant Colic and the Multi-Omic Composition of Human Milk

Multi-omics integration identifies regulatory factors underlying bovine subclinical mastitis

Multi-omics integration identifies regulatory factors underlying bovine subclinical mastitis

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