Oral Administration of Bovine Milk‐Derived Extracellular Vesicles Alters the Gut Microbiota and Enhances Intestinal Immunity in Mice

Tong, Lingjun; Hao, Haining; Zhang, Xinyi; Zhang, Zhe; Lv, Yan; Zhang, Lanwei; Yi, Huaxi

doi:10.1002/mnfr.201901251

Cited by 76 publications

(97 citation statements)

References 73 publications

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“…Precisely, mucus production by goblet cells and increased levels of sIgA were reported to be some of the mechanisms of probiotic action in the host (Rogier et al, 2014). Interestingly, dairy milk can significantly induce the host response to pathogens, enhance the integrity of the mucus layer (Tong et al, 2020), and increase secretory IgA in the small and large intestines (Schofield and Palm, 2018). In our previous works, we verified that dairy milk matrices, including cheese matrix, can increase IgA secretion (Cordeiro et al, 2018Rabah et al, 2020, while the milk matrix shows an increase in the number of goblet cells (Cordeiro et al, 2018).…”

Section: Discussionsupporting

confidence: 56%

Therapeutic Effects of Probiotic Minas Frescal Cheese on the Attenuation of Ulcerative Colitis in a Murine Model

et al. 2021

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Inflammatory bowel diseases (IBDs) constitute disturbances of gastrointestinal tract that cause irreversible changes in the structure and function of tissues. Ulcerative colitis (UC), the most frequent IBD in the population, is characterized by prominent inflammation of the human colon. Functional foods containing probiotic bacteria have been studied as adjuvants to the treatment or prevention of IBDs. The selected probiotic strain Lactococcus lactis NCDO 2118 (L. lactis NCDO 2118) exhibits immunomodulatory effects, with promising results in UC mouse model induced by dextran sodium sulfate (DSS). Additionally, cheese is a dairy food that presents high nutritional value, besides being a good delivery system that can be used to improve survival and enhance the therapeutic effects of probiotic bacteria in the host. Therefore, this work investigated the probiotic therapeutic effects of an experimental Minas Frescal cheese containing L. lactis NCDO 2118 in DSS-induced colitis in mice. During colitis induction, mice that consumed the probiotic cheese exhibited reduced in the severity of colitis, with attenuated weight loss, lower disease activity index, limited shortening of the colon length, and reduced histopathological score. Moreover, probiotic cheese administration increased gene expression of tight junctions’ proteins zo-1, zo-2, ocln, and cln-1 in the colon and increase IL-10 release in the spleen and lymph nodes. In this way, this work demonstrates that consumption of probiotic Minas Frescal cheese, containing L. lactis NCDO 2118, prevents the inflammatory process during DSS-induced colitis in mice, opening perspectives for the development of new probiotic functional foods for personalized nutrition in the context of IBD.

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Section: Discussionsupporting

confidence: 56%

Therapeutic Effects of Probiotic Minas Frescal Cheese on the Attenuation of Ulcerative Colitis in a Murine Model

et al. 2021

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“…For instance, the role of bovine milk EV cargo has been highlighted in being able to elicit changes in microflora in mice cecum [ 162 ]. Further, these vesicles could also interact with the microbiota and modulate their metabolites [ 163 ]. Another such study has revealed the ability of bovine milk EVs to restore the healthy gut bacteria and alleviate colitis induced dysbiosis [ 147 ].…”

Section: Milk Evs In Cross-organism and Cross-species Communicatiomentioning

confidence: 99%

Milk-Derived Extracellular Vesicles in Inter-Organism, Cross-Species Communication and Drug Delivery

et al. 2020

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Milk is considered as more than a source of nutrition for infants and is a vector involved in the transfer of bioactive compounds and cells. Milk contains abundant quantities of extracellular vesicles (EVs) that may originate from multiple cellular sources. These nanosized vesicles have been well characterized and are known to carry a diverse cargo of proteins, nucleic acids, lipids and other biomolecules. Milk-derived EVs have been demonstrated to survive harsh and degrading conditions in gut, taken up by various cell types, cross biological barriers and reach peripheral tissues. The cargo carried by these dietary EVs has been suggested to have a role in cell growth, development, immune modulation and regulation. Hence, there is considerable interest in understanding the role of milk-derived EVs in mediating inter-organismal and cross-species communication. Furthermore, various attributes such as it being a natural source, as well as its abundance, scalability, economic viability and lack of unwarranted immunologic reactions, has generated significant interest in deploying milk-derived EVs for clinical applications such as drug delivery and disease therapy. In this review, the role of milk-derived EVs in inter-organismal, cross-species communication and in drug delivery is discussed.

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“…In the last decade, the number of studies reporting the isolation of EVs from foods (both from plant and animal origin) has increased substantially [ 10 , 11 ]. In particular, milk is a major source of EVs and their cargos may have a bioactive role in the consumer’s health [ 12 , 13 , 14 , 15 , 16 ].…”

Section: Introductionmentioning

confidence: 99%

Bovine Milk-Derived Exosomes as a Drug Delivery Vehicle for miRNA-Based Therapy

Pozo-Acebo

Hazas

Tomé‐Carneiro

et al. 2021

IJMS

100

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MicroRNAs (miRNAs) are small non-coding RNAs with a known role as mediators of gene expression in crucial biological processes, which converts them into high potential contenders in the ongoing search for effective therapeutic strategies. However, extracellular RNAs are unstable and rapidly degraded, reducing the possibility of successfully exerting a biological function in distant target cells. Strategies aimed at enhancing the therapeutic potential of miRNAs include the development of efficient, tissue-specific and nonimmunogenic delivery methods. Since miRNAs were discovered to be naturally transported within exosomes, a type of extracellular vesicle that confers protection against RNase degradation and increases miRNA stability have been proposed as ideal delivery vehicles for miRNA-based therapy. Although research in this field has grown rapidly in the last few years, a standard, reproducible and cost-effective protocol for exosome isolation and extracellular RNA delivery is lacking. We aimed to evaluate the use of milk-derived extracellular vesicles as vehicles for extracellular RNA drug delivery. With this purpose, exosomes were isolated from raw bovine milk, combining ultracentrifugation and size exclusion chromatography (SEC) methodology. Isolated exosomes were then loaded with exogenous hsa-miR148a-3p, a highly expressed miRNA in milk exosomes. The suitability of exosomes as delivery vehicles for extracellular RNAs was tested by evaluating the absorption of miR-148a-3p in hepatic (HepG2) and intestinal (Caco-2) cell lines. The potential exertion of a biological effect by miR-148a-3p was assessed by gene expression analysis, using microarrays. Results support that bovine milk is a cost-effective source of exosomes which can be used as nanocarriers of functional miRNAs with a potential use in RNA-based therapy. In addition, we show here that a combination of ultracentrifugation and SEC technics improve exosome enrichment, purity, and integrity for subsequent use.

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Oral Administration of Bovine Milk‐Derived Extracellular Vesicles Alters the Gut Microbiota and Enhances Intestinal Immunity in Mice

Cited by 76 publications

References 73 publications

Therapeutic Effects of Probiotic Minas Frescal Cheese on the Attenuation of Ulcerative Colitis in a Murine Model

Therapeutic Effects of Probiotic Minas Frescal Cheese on the Attenuation of Ulcerative Colitis in a Murine Model

Milk-Derived Extracellular Vesicles in Inter-Organism, Cross-Species Communication and Drug Delivery

Bovine Milk-Derived Exosomes as a Drug Delivery Vehicle for miRNA-Based Therapy

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