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Keywords = entero-mammary pathway

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22 pages, 2098 KB  
Review
Mammary Gland Microbiota in Benign Breast Diseases
by Nikita I. Ukraincev, Maria I. Kashutina, Larisa I. Kasatkina, Adkhamzhon B. Abduraimov and Yury V. Zhernov
Int. J. Mol. Sci. 2025, 26(20), 9951; https://doi.org/10.3390/ijms26209951 - 13 Oct 2025
Viewed by 1210
Abstract
The human microbiome is a critical factor in health and disease. While its association with breast cancer (BC) has been increasingly studied, this review provides a dedicated synthesis of the microbiota’s role in benign breast diseases (BBDs)—a common yet microbiologically overlooked spectrum of [...] Read more.
The human microbiome is a critical factor in health and disease. While its association with breast cancer (BC) has been increasingly studied, this review provides a dedicated synthesis of the microbiota’s role in benign breast diseases (BBDs)—a common yet microbiologically overlooked spectrum of conditions. The primary aim of this work is to consolidate the current understanding of the composition, origins, and functional mechanisms of the mammary gland (MG) microbiota specifically in the context of BBD and to evaluate its potential for novel diagnostic and therapeutic targets. We detail the distinct MG microbiota, formed via exogenous (e.g., cutaneous, translocation) and endogenous (e.g., enteromammary, lymphohematogenous) pathways, and its interaction with the host through estrogen metabolism, immunomodulation, and epigenetic modifications. This narrative review reveals unique dysbiotic patterns in BBD, characterized by distinct microbial signatures, such as the enrichment of Corynebacterium kroppenstedtii in granulomatous mastitis and the presence of Staphylococcus aureus in fibroadenomas and lactational mastitis. Furthermore, specific gut microbial profiles are identified in BBD patients, including an increased abundance of genera such as Clostridium and Faecalibacterium, alongside a decrease in Collinsella and Alistipes compared to healthy controls. These specific taxa represent compelling candidates for diagnostic biomarkers. We conclude that microbial dysbiosis is a significant component of BBD pathogenesis. A paradigm shift toward multi-omics approaches and mechanistic studies is now essential to translate these associations into clinical applications. Understanding the BBD-specific microbiome holds the promise of revolutionizing patient care through microbiota-based diagnostics for differentiating benign subtypes and novel, personalized therapeutic strategies aimed at restoring microbial homeostasis. Full article
(This article belongs to the Section Molecular Microbiology)
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32 pages, 407 KB  
Review
The Influence of Maternal Lifestyle Factors on Human Breast Milk Microbial Composition: A Narrative Review
by Irene Bianco, Chiara Ferrara, Francesca Romano, Federica Loperfido, Francesca Sottotetti, Dana El Masri, Alessandra Vincenti, Hellas Cena and Rachele De Giuseppe
Biomedicines 2024, 12(11), 2423; https://doi.org/10.3390/biomedicines12112423 - 22 Oct 2024
Cited by 9 | Viewed by 6372
Abstract
Human breast milk (HBM) is considered the gold standard for infant nutrition due to its optimal nutrient profile and complex composition of cellular and non-cellular components. Breastfeeding positively influences the newborn’s gut microbiota and health, reducing the risk of conditions like gastrointestinal infections [...] Read more.
Human breast milk (HBM) is considered the gold standard for infant nutrition due to its optimal nutrient profile and complex composition of cellular and non-cellular components. Breastfeeding positively influences the newborn’s gut microbiota and health, reducing the risk of conditions like gastrointestinal infections and chronic diseases (e.g., allergies, asthma, diabetes, and obesity). Research has revealed that HBM contains beneficial microbes that aid gut microbiota maturation through mechanisms like antimicrobial production and pathogen exclusion. The HBM microbiota composition can be affected by several factors, including gestational age, delivery mode, medical treatments, lactation stage, as well as maternal lifestyle habits (e.g., diet, physical activity, sleep quality, smoking, alcohol consumption, stress level). Particularly, lifestyle factors can play a significant role in shaping the HBM microbiota by directly modulating the microbial composition or influencing the maternal gut microbiota and influencing the HBM microbes through the enteromammary pathway. This narrative review of current findings summarized how maternal lifestyle influences HBM microbiota. While the influence of maternal diet on HBM microbiota is well-documented, indicating that dietary patterns, especially those rich in plant-based proteins and complex carbohydrates, can positively influence HBM microbiota, the impact of other lifestyle factors is poorly investigated. Maintaining a healthy lifestyle during pregnancy and breastfeeding is crucial for the health of both mother and baby. Understanding how maternal lifestyle factors influence microbial colonization of HBM, along with their interactions and impact, is key to developing new strategies that support the beneficial maturation of the infant’s gut microbiota. Full article
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20 pages, 813 KB  
Review
Drinking Water Microbiota, Entero-Mammary Pathways, and Breast Cancer: Focus on Nontuberculous Mycobacteria
by Ana Maranha, Susana Alarico, Daniela Nunes-Costa, Inês Melo-Marques, Inês Roxo, Pedro Castanheira, Olga Caramelo and Nuno Empadinhas
Microorganisms 2024, 12(7), 1425; https://doi.org/10.3390/microorganisms12071425 - 13 Jul 2024
Cited by 2 | Viewed by 4495
Abstract
The prospect of drinking water serving as a conduit for gut bacteria, artificially selected by disinfection strategies and a lack of monitoring at the point of use, is concerning. Certain opportunistic pathogens, notably some nontuberculous mycobacteria (NTM), often exceed coliform bacteria levels in [...] Read more.
The prospect of drinking water serving as a conduit for gut bacteria, artificially selected by disinfection strategies and a lack of monitoring at the point of use, is concerning. Certain opportunistic pathogens, notably some nontuberculous mycobacteria (NTM), often exceed coliform bacteria levels in drinking water, posing safety risks. NTM and other microbiota resist chlorination and thrive in plumbing systems. When inhaled, opportunistic NTM can infect the lungs of immunocompromised or chronically ill patients and the elderly, primarily postmenopausal women. When ingested with drinking water, NTM often survive stomach acidity, reach the intestines, and migrate to other organs using immune cells as vehicles, potentially colonizing tumor tissue, including in breast cancer. The link between the microbiome and cancer is not new, yet the recognition of intratumoral microbiomes is a recent development. Breast cancer risk rises with age, and NTM infections have emerged as a concern among breast cancer patients. In addition to studies hinting at a potential association between chronic NTM infections and lung cancer, NTM have also been detected in breast tumors at levels higher than normal adjacent tissue. Evaluating the risks of continued ingestion of contaminated drinking water is paramount, especially given the ability of various bacteria to migrate from the gut to breast tissue via entero-mammary pathways. This underscores a pressing need to revise water safety monitoring guidelines and delve into hormonal factors, including addressing the disproportionate impact of NTM infections and breast cancer on women and examining the potential health risks posed by the cryptic and unchecked microbiota from drinking water. Full article
(This article belongs to the Special Issue Advances in Waterborne Pathogens)
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24 pages, 18025 KB  
Article
Post Natal Microbial and Metabolite Transmission: The Path from Mother to Infant
by Juan Manuel Vélez-Ixta, Carmen Josefina Juárez-Castelán, Daniela Ramírez-Sánchez, Noemí del Socorro Lázaro-Pérez, José Javier Castro-Arellano, Silvia Romero-Maldonado, Enrique Rico-Arzate, Carlos Hoyo-Vadillo, Marisol Salgado-Mancilla, Carlos Yamel Gómez-Cruz, Aparna Krishnakumar, Alberto Piña-Escobedo, Tizziani Benitez-Guerrero, María Luisa Pizano-Zárate, Yair Cruz-Narváez and Jaime García-Mena
Nutrients 2024, 16(13), 1990; https://doi.org/10.3390/nu16131990 - 22 Jun 2024
Cited by 11 | Viewed by 3490
Abstract
The entero–mammary pathway is a specialized route that selectively translocates bacteria to the newborn’s gut, playing a crucial role in neonatal development. Previous studies report shared bacterial and archaeal taxa between human milk and neonatal intestine. However, the functional implications for neonatal development [...] Read more.
The entero–mammary pathway is a specialized route that selectively translocates bacteria to the newborn’s gut, playing a crucial role in neonatal development. Previous studies report shared bacterial and archaeal taxa between human milk and neonatal intestine. However, the functional implications for neonatal development are not fully understood due to limited evidence. This study aimed to identify and characterize the microbiota and metabolome of human milk, mother, and infant stool samples using high-throughput DNA sequencing and FT-ICR MS methodology at delivery and 4 months post-partum. Twenty-one mothers and twenty-five infants were included in this study. Our results on bacterial composition suggest vertical transmission of bacteria through breastfeeding, with major changes occurring during the first 4 months of life. Metabolite chemical characterization sheds light on the growing complexity of the metabolites. Further data integration and network analysis disclosed the interactions between different bacteria and metabolites in the biological system as well as possible unknown pathways. Our findings suggest a shared bacteriome in breastfed mother–neonate pairs, influenced by maternal lifestyle and delivery conditions, serving as probiotic agents in infants for their healthy development. Also, the presence of food biomarkers in infants suggests their origin from breast milk, implying selective vertical transmission of these features. Full article
(This article belongs to the Section Prebiotics, Probiotics and Postbiotics)
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15 pages, 1779 KB  
Article
A Stress Reduction Intervention for Lactating Mothers Alters Maternal Gut, Breast Milk, and Infant Gut Microbiomes: Data from a Randomized Controlled Trial
by Jinyue Yu, Yan Zhang, Jonathan C. K. Wells, Zhuang Wei, Mona Bajaj-Elliott, Dennis Sandris Nielsen and Mary S. Fewtrell
Nutrients 2024, 16(7), 1074; https://doi.org/10.3390/nu16071074 - 6 Apr 2024
Cited by 3 | Viewed by 4107
Abstract
Background: This secondary analysis of data from a randomized controlled trial (RCT) investigated how the maternal gut, breast milk, and infant gut microbiomes may contribute to the effects of a relaxation intervention, which reduced maternal stress and promoted infant weight gain. Methods: An [...] Read more.
Background: This secondary analysis of data from a randomized controlled trial (RCT) investigated how the maternal gut, breast milk, and infant gut microbiomes may contribute to the effects of a relaxation intervention, which reduced maternal stress and promoted infant weight gain. Methods: An RCT was undertaken in healthy Chinese primiparous mother–infant pairs (340/7–376/7gestation weeks). Mothers were randomly allocated to either the intervention group (IG, listening to relaxation meditation) or the control group (CG). Outcomes were the differences in microbiome composition and the diversity in the maternal gut, breast milk, and infant gut at 1 (baseline) and 8 weeks (post-intervention) between IG and CG, assessed using 16S rRNA gene amplicon sequencing of fecal and breastmilk samples. Results: In total, 38 mother–infant pairs were included in this analysis (IG = 19, CG = 19). The overall microbiome community structure in the maternal gut was significantly different between the IG and CG at 1 week, with the difference being more significant at 8 weeks (Bray–Curtis distance R2 = 0.04 vs. R2 = 0.13). Post-intervention, a significantly lower α-diversity was observed in IG breast milk (observed features: CG = 295 vs. IG = 255, p = 0.032); the Bifidobacterium genera presented a higher relative abundance. A significantly higher α-diversity was observed in IG infant gut (observed features: CG = 73 vs. IG = 113, p < 0.001). Conclusions: The findings were consistent with the hypothesis that the microbiome might mediate observed relaxation intervention effects via gut–brain axis and entero-mammary pathways; but confirmation is required. Full article
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21 pages, 2902 KB  
Article
The Entero-Mammary Pathway and Perinatal Transmission of Gut Microbiota and SARS-CoV-2
by Carmen Josefina Juárez-Castelán, Juan Manuel Vélez-Ixta, Karina Corona-Cervantes, Alberto Piña-Escobedo, Yair Cruz-Narváez, Alejandro Hinojosa-Velasco, María Esther Landero-Montes-de-Oca, Eduardo Davila-Gonzalez, Eduardo González-del-Olmo, Fernando Bastida-Gonzalez, Paola Berenice Zárate-Segura and Jaime García-Mena
Int. J. Mol. Sci. 2022, 23(18), 10306; https://doi.org/10.3390/ijms231810306 - 7 Sep 2022
Cited by 15 | Viewed by 4839
Abstract
COVID-19 is a severe respiratory disease threatening pregnant women, which increases the possibility of adverse pregnancy outcomes. Several recent studies have demonstrated the ability of SARS-CoV-2 to infect the mother enterocytes, disturbing the gut microbiota diversity. The aim of this study was to [...] Read more.
COVID-19 is a severe respiratory disease threatening pregnant women, which increases the possibility of adverse pregnancy outcomes. Several recent studies have demonstrated the ability of SARS-CoV-2 to infect the mother enterocytes, disturbing the gut microbiota diversity. The aim of this study was to characterize the entero-mammary microbiota of women in the presence of the virus during delivery. Fifty mother–neonate pairs were included in a transversal descriptive work. The presence of SARS-CoV-2 RNA was detected in nasopharyngeal, mother rectal swabs (MRS) and neonate rectal swabs (NRS) collected from the pairs, and human colostrum (HC) samples collected from mothers. The microbiota diversity was characterized by high-throughput DNA sequencing of V3-16S rRNA gene libraries prepared from HC, MRS, and NRS. Data were analyzed with QIIME2 and R. Our results indicate that several bacterial taxa are highly abundant in MRS positive for SARS-CoV-2 RNA. These bacteria mostly belong to the Firmicutes phylum; for instance, the families Bifidobacteriaceae, Oscillospiraceae, and Microbacteriaceae have been previously associated with anti-inflammatory effects, which could explain the capability of women to overcome the infection. All samples, both positive and negative for SARS-CoV-2, featured a high abundance of the Firmicutes phylum. Further data analysis showed that nearly 20% of the bacterial diversity found in HC was also identified in MRS. Spearman correlation analysis highlighted that some genera of the Proteobacteria and Actinobacteria phyla were negatively correlated with MRS and NRS (p < 0.005). This study provides new insights into the gut microbiota of pregnant women and their potential association with a better outcome during SARS-CoV-2 infection. Full article
(This article belongs to the Special Issue COVID-19 and Future Pathogens)
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25 pages, 2192 KB  
Review
An Insight into Probiotics Bio-Route: Translocation from the Mother’s Gut to the Mammary Gland
by Shanmugaprakasham Selvamani, Daniel Joe Dailin, Vijai Kumar Gupta, Mohd Wahid, Ho Chin Keat, Khairun Hani Natasya, Roslinda Abd Malek, Shafiul Haque, R. Z. Sayyed, Bassam Abomoelak, Dalia Sukmawati, Theodoros Varzakas and Hesham Ali El Enshasy
Appl. Sci. 2021, 11(16), 7247; https://doi.org/10.3390/app11167247 - 6 Aug 2021
Cited by 28 | Viewed by 10612
Abstract
Human breast milk (HBM) is unique in its composition as it is adapted to fulfil the newborns’ nutritional requirement and helps in improving the health of newborns. Besides various nutrients, the human milk also contains diverse group of microbiotas. The human milk microbiota [...] Read more.
Human breast milk (HBM) is unique in its composition as it is adapted to fulfil the newborns’ nutritional requirement and helps in improving the health of newborns. Besides various nutrients, the human milk also contains diverse group of microbiotas. The human milk microbiota has a remarkable impact on the growth and development of a newborn. Additionally, the human milk microbiota enhances the colonization of microbes in the gut of infants. Debates about the origin of HBM microbial flora remain premature and contradictory in some cases. Recent data suggest that the maternal gut microbiota has a major impact on microbial composition, areolar skin, and from the infant’s oral cavity. The current review investigates the possible route of microbial transfer from the maternal gut to mammary gland and suggests that it might occur through the entero-mammary pathway. It involves precise selection of probiotic microorganisms from the gut, as the human gut hosts trillions of microorganisms involved in gut homeostasis and other metabolic pathways. Gastrointestinal lymphatic vessels, macrophages, and dendritic cells are shown to play a significant role in the microbial transmission. Furthermore, the role of microbial factors in the development of neonatal immunity and translocation of secretory IgA (SIgA) cells from the intestinal lumen to GALT and finally to mammary glands via entero-mammary link are discussed. Full article
(This article belongs to the Special Issue New Insights in Oral Health and Diets)
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14 pages, 1393 KB  
Article
Characterization of Microbiome on Feces, Blood and Milk in Dairy Cows with Different Milk Leucocyte Pattern
by Elisa Scarsella, Alfonso Zecconi, Michela Cintio and Bruno Stefanon
Animals 2021, 11(5), 1463; https://doi.org/10.3390/ani11051463 - 19 May 2021
Cited by 35 | Viewed by 4992
Abstract
Mastitis is an inflammatory disease of the mammary gland, caused by the invasion of microorganism on this site, associated with an altered immune response. Recent studies in this field hypothesize that the origin of these pathogens can also be from the gastrointestinal tract, [...] Read more.
Mastitis is an inflammatory disease of the mammary gland, caused by the invasion of microorganism on this site, associated with an altered immune response. Recent studies in this field hypothesize that the origin of these pathogens can also be from the gastrointestinal tract, through the entero-mammary pathway in relation to an increase in gut permeability. In this study, we wanted to investigate if inflammatory status of the mammary gland is related to an alteration of gut permeability. The microbiome of feces, blood and milk of lactating cows, recruited on the basis of the total somatic cell count and of the percentage of polymorphonuclear neutrophils and lymphocytes, was studied. Cows were divided into healthy (G), at risk of mastitis (Y) and with mastitis (R) classifications. The bacterial DNA was extracted and the V3 and V4 regions of 16S rRNA sequenced. Moreover, the quantification of total bacteria was performed with quantitative real-time PCR. A non-parametric Kruskal–Wallis test was applied at the phylum, family and genera levels and beta biodiversity was evaluated with the unweighted UniFrac distance metric. Significant differences between groups were found for the microbial composition of feces (Clostridiaceae, Turicibacteriaceae for family level and Clostridium, Dorea, SMB53 and Turicibacter for genus level), blood (Tenericutes for phylum level and Mycoplasma for genus level) and milk (OD1 and Proteobacteria for phylum level, Enterobacteriaceae and Moraxallaceae for family level and Olsenella and Rhodococcus for genus level). The beta biodiversity of feces and blood did not change between groups. Significant differences (p < 0.05) were observed between the beta diversity in milk of G group and Y group and between Y group and R group. The number of taxa in common between feces, blood and milk were 8 at a phylum, 19 at a family and 15 at a genus level. From these results, the bacterial crossing from gut to milk in cows was not confirmed but remained hypothetical and deserves further investigation. Full article
(This article belongs to the Section Veterinary Clinical Studies)
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23 pages, 1517 KB  
Review
The Gut‒Breast Axis: Programming Health for Life
by Juan M. Rodríguez, Leónides Fernández and Valerie Verhasselt
Nutrients 2021, 13(2), 606; https://doi.org/10.3390/nu13020606 - 12 Feb 2021
Cited by 84 | Viewed by 10869
Abstract
The gut is a pivotal organ in health and disease. The events that take place in the gut during early life contribute to the programming, shaping and tuning of distant organs, having lifelong consequences. In this context, the maternal gut plays a quintessence [...] Read more.
The gut is a pivotal organ in health and disease. The events that take place in the gut during early life contribute to the programming, shaping and tuning of distant organs, having lifelong consequences. In this context, the maternal gut plays a quintessence in programming the mammary gland to face the nutritional, microbiological, immunological, and neuroendocrine requirements of the growing infant. Subsequently, human colostrum and milk provides the infant with an impressive array of nutrients and bioactive components, including microbes, immune cells, and stem cells. Therefore, the axis linking the maternal gut, the breast, and the infant gut seems crucial for a correct infant growth and development. The aim of this article is not to perform a systematic review of the human milk components but to provide an insight of their extremely complex interactions, which render human milk a unique functional food and explain why this biological fluid still truly remains as a scientific enigma. Full article
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30 pages, 812 KB  
Review
Breast Milk, a Source of Beneficial Microbes and Associated Benefits for Infant Health
by Katríona E. Lyons, C. Anthony Ryan, Eugene M. Dempsey, R. Paul Ross and Catherine Stanton
Nutrients 2020, 12(4), 1039; https://doi.org/10.3390/nu12041039 - 9 Apr 2020
Cited by 457 | Viewed by 247110
Abstract
Human breast milk is considered the optimum feeding regime for newborn infants due to its ability to provide complete nutrition and many bioactive health factors. Breast feeding is associated with improved infant health and immune development, less incidences of gastrointestinal disease and lower [...] Read more.
Human breast milk is considered the optimum feeding regime for newborn infants due to its ability to provide complete nutrition and many bioactive health factors. Breast feeding is associated with improved infant health and immune development, less incidences of gastrointestinal disease and lower mortality rates than formula fed infants. As well as providing fundamental nutrients to the growing infant, breast milk is a source of commensal bacteria which further enhance infant health by preventing pathogen adhesion and promoting gut colonisation of beneficial microbes. While breast milk was initially considered a sterile fluid and microbes isolated were considered contaminants, it is now widely accepted that breast milk is home to its own unique microbiome. The origins of bacteria in breast milk have been subject to much debate, however, the possibility of an entero-mammary pathway allowing for transfer of microbes from maternal gut to the mammary gland is one potential pathway. Human milk derived strains can be regarded as potential probiotics; therefore, many studies have focused on isolating strains from milk for subsequent use in infant health and nutrition markets. This review aims to discuss mammary gland development in preparation for lactation as well as explore the microbial composition and origins of the human milk microbiota with a focus on probiotic development. Full article
(This article belongs to the Special Issue Human Milk, HMO, Lactation and Application in Infant Feeding)
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