Xeno-miRNA in Maternal-Infant Immune Crosstalk: An Aid to Disease Alleviation

Stephen, Bjorn John; Pareek, Nidhi; Kausar, Mohd Adnan; Rahman, Safikur; Datta, Manali

doi:10.3389/fimmu.2020.00404

Cited by 26 publications

(20 citation statements)

References 71 publications

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“…Compared to other body fluids, breast milk is exceptionally rich in RNA ( 15 ); and many of the miRNAs found in breast milk are seemingly involved in modulating immunological pathways ( 16 ). Moreover, xeno-miRNA exhibiting maternal-infant immune cross-talk has also been found ( 17 ).…”

Section: Introductionmentioning

confidence: 99%

Non-Coding RNAs in Human Breast Milk: A Systematic Review

et al. 2021

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Breast milk is the primary source of nutrition and hydration for the newborn infant but also plays an important role in the child’s first immune defense. Additionally, several breast milk factors have been implicated in immune-related health outcomes later in life, including immunoglobulins, cytokines, chemokines, growth factors and, more recently, non-coding RNA (ncRNA) species. In this systematic review, we provide a comprehensive summary of the current literature on endogenous ncRNAs found in human breast milk. Thirty (30) relevant studies were identified and, whilst the majority studies focused on microRNAs (miRNAs), there is evidence that breast milk contains high quantities of RNA which also include long-coding RNAs, circular RNAs, as well as other short RNAs and fragmented tRNA and rRNAs. Among studies investigating miRNAs, miR-148a-3p, miR-30a/d-5p, miR-22-3p, miR-146b-5p, miR-200a/c-3p, and the 5p end of the let-7 miRNAs were commonly reported among the top 10 miRNAs in the cell, lipid, and skim milk fractions of breast milk. Methodological difference and small sample sizes limit the possibility of conclusively identifying which maternal and infant characteristics affect the miRNA profile. The highly expressed miRNAs were generally reported to be similar across lactational stage, milk fraction, maternal and infant characteristics, or infant growth and health. All the same, individual studies identify potential differences in miRNA expression levels which should be confirmed by future studies. Stability, uptake, and physiological functions of miRNAs were also considered in several studies. Breast milk miRNAs are relatively resistant to a range of harsh conditions and uptake experiments suggest that extracellular vesicles containing miRNAs and circular RNAs can be taken up by intestinal epithelial cells. Although the evidence regarding the functional effect of breast milk miRNAs is limited, the predicted functions range from metabolic and biosynthetic processes to signaling pathways, cellular adhesion, communication, growth, and differentiation. Finally, this systematic review highlights some of the methodological challenges and knowledge gaps which can help direct future research in this field. In particular, it is important to further investigate the bioavailability of miRNAs in different milk fractions, and to characterize other ncRNAs which are largely unstudied.Systematic Review RegistrationPROSPERO https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=138989, identifier CRD42020138989.

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Section: Introductionmentioning

confidence: 99%

Non-Coding RNAs in Human Breast Milk: A Systematic Review

et al. 2021

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“…Notably, there is accumulative evidence showing that milkderived extracellular vesicles contain plant miRNAs (191,192), suggesting that eventually, immune system shaping might be attributed to xenomiRs. Indeed, it has been pointed out that plant miRNAs acquired through diet could be captured by human mammary glands, packaged into exosomes and transmitted through milk to infants (193). However, further research is required to determine if plant miRNAs could play part in the immunomodulatory effects assigned so far to milk-derived exosomes (194)(195)(196)(197).…”

Section: Relevance Of Xenomirs On Intestinal Permeability Through Modulation Of Immune System Functionsmentioning

confidence: 99%

Potential Mechanisms Linking Food-Derived MicroRNAs, Gut Microbiota and Intestinal Barrier Functions in the Context of Nutrition and Human Health

et al. 2021

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MicroRNAs (miRNAs) are non-coding single-stranded RNA molecules from 18 to 24 nucleotides that are produced by prokaryote and eukaryote organisms, which play a crucial role in regulating gene expression through binding to their mRNA targets. MiRNAs have acquired special attention for their potential in cross kingdom communication, notably food-derived microRNAs (xenomiRs), which could have an impact on microorganism and mammal physiology. In this review, we mainly aim to deal with new perspectives on: (1) The mechanism by which food-derived xenomiRs (mainly dietary plant xenomiRs) could be incorporated into humans through diet, in a free form, associated with proteins or encapsulated in exosome-like nanoparticles. (2) The impact of dietary plant-derived miRNAs in modulating gut microbiota composition, which in turn, could regulate intestinal barrier permeability and therefore, affect dietary metabolite, postbiotics or food-derived miRNAs uptake efficiency. Individual gut microbiota signature/composition could be also involved in xenomiR uptake efficiency through several mechanisms such us increasing the bioavailability of exosome-like nanoparticles miRNAs. (3) Gut microbiota dysbiosis has been proposed to contribute to disease development by affecting gut epithelial barrier permeability. For his reason, the availability and uptake of dietary plant xenomiRs might depend, among other factors, on this microbiota-related permeability of the intestine. We hypothesize and critically review that xenomiRs-microbiota interaction, which has been scarcely explored yet, could contribute to explain, at least in part, the current disparity of evidences found dealing with dietary miRNA uptake and function in humans. Furthermore, dietary plant xenomiRs could be involved in the establishment of the multiple gut microenvironments, in which microorganism would adapt in order to optimize the resources and thrive in them. Additionally, a particular xenomiR could preferentially accumulate in a specific region of the gastrointestinal tract and participate in the selection and functions of specific gut microbial communities.

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“…In circulatory system, these miRNAs are mainly present in extracellular vesicles, such as the exosomes (extracellular vesicles of endosomal origin), and are emerging as the key mediators of intercellular communication [10]. On further screening of these cmiRNAs, some of them were identified to be from exogenous species [11]. These special groups of miRNAs were categorized as…”

Section: Introductionmentioning

confidence: 99%

“…xenomiRs. Some of these xenomiRs have found to enter the host through food ingestion; like breast milk from mother to infant may modulate the immune system of new-borns through dietary miRNA present in milk [11] .This gives rise to a new concept of food-derived miRNAs or dietary miRNAs. Zhang et al were the first group to report that exogenous miRNA miR168a can be absorbed in the GI, enter the peripheral bloodstream, uptake by host cells, and exert LDLRAP1 gene regulation to reduce its expression, leading to elevation of mouse blood LDL levels [12].…”

Section: Introductionmentioning

confidence: 99%

<strong>Diet-Derived Exogenous miRNAs As Functional Food Components: Facts and New Perspectives</strong>

Khurana¹,

Gupta²,

Varshney³

2021

Preprint

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Exogenous miRNAs derived from dietary substances have been shown to be orally transferred to the mammalian system and proven to remain active to regulate host-gene expression. This way they have become an active area of research as functional food components and aspects for dietary supplementation. They are being studied as a new class of metabolically targeted therapeutics that work through diet manipulation and may hold promise for a therapeutic approach in reducing the risk of life-threatening diseases. However, a substantial amount of evidence also defies this dietary miRNA concept in terms of their absorption, bioavailability, cellular uptake and its physiological effects in the mammalian system. But recent advances in the identification of some unique sequence and structural characteristics of dietary miRNAs and a deeper understanding of their stability in host peripheral blood for its cellular uptake have strengthened the whole concept. The review comprehensively summarizes the mechanism for miRNA extracellular transport, absorption through the gastrointestinal tract (GI), stability in peripheral blood, and cellular uptake in mammalian cells. It recapitulates the shreds of evidence, related to the influence of dietary miRNAs on gene expression based on the source of the origin (plant vs animal), and compares their cross-kingdom behaviour in terms of their unique sequence and stem-loop structure properties that help them to get stabilized in the mammalian system. The review also summarizes the parameters required for maintaining the sustainable uptake and bioavailability of the dietary miRNAs with existing examples of successful in-vivo and in-vitro delivery of dietary miRNA for augmented therapy. Lastly, it provides an overview of the available and required databases, webserver, and tools that can be used for the successful identification of potential dietary miRNA candidates.

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Xeno-miRNA in Maternal-Infant Immune Crosstalk: An Aid to Disease Alleviation

Cited by 26 publications

References 71 publications

Non-Coding RNAs in Human Breast Milk: A Systematic Review

Non-Coding RNAs in Human Breast Milk: A Systematic Review

Potential Mechanisms Linking Food-Derived MicroRNAs, Gut Microbiota and Intestinal Barrier Functions in the Context of Nutrition and Human Health

<strong>Diet-Derived Exogenous miRNAs As Functional Food Components: Facts and New Perspectives</strong>

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