Pro-inflammatory cytokines and growth factors in human milk: an exploratory analysis of racial differences to inform breast cancer etiology

Murphy, Jeanne; Pfeiffer, Ruth M.; Lynn, Brittny C. Davis; Caballero, Ana I.; Browne, Eva P.; Punska, Elizabeth C.; Yang, Hannah; Falk, Roni T.; Anderton, Douglas L.; Gierach, Gretchen L.; Arcaro, Kathleen F.; Sherman, Mark E.

doi:10.1007/s10549-018-4907-7

Cited by 17 publications

(38 citation statements)

References 41 publications

(38 reference statements)

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“…These factors may affect the cytokine levels of human milk. In previous study, elevated maternal BMI was significantly associated with increased levels of some kind of cytokines in their milk (20). In this study, these factors showed similar values between the two groups except for IgA.…”

Section: Discussionmentioning

confidence: 86%

Effects of Probiotic Supplementation on TGF-β1, TGF-β2, and IgA Levels in the Milk of Japanese Women: An Open-Label Pilot Study

et al. 2019

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Background: Dietary probiotics supplementation in lactating mothers may help prevent allergic disease in infants. However, owing to a lack of consistency in nutritional and safety outcomes associated with probiotics, this topic remains controversial.Methods: In this open-label pilot trial conducted between April 2013 and December 2013, we evaluated the safety of probiotic supplementation with 5 × 109 CFU of Lactobacillus casei LC5, 5 × 109 CFU of Bifidobacterium longum BG7, and 2 × 108 CFU of Bacillus coagulans SANK70258 in lactating women who exhibited allergies for 2 months (1–3 months postpartum); we also evaluated the effects of probiotic supplementation on transforming growth factor-β (TGF-β) and immunoglobulin A (IgA) levels in human milk. Participants self-selected to join the probiotic (n = 41; age [median (interquartile range [IQR]), y] 33 [27–39], body mass index [BMI] [median (IQR), kg/m2] 21.8 [19.5–22.8]) or no supplementation control group (n = 19; age [median (IQR), y] 33 [23–43], BMI [median (IQR), kg/m2) 19.6 [18.4–22.1]). Probiotics (three tablets) received were taken as daily supplements. Milk samples were collected at 1, 2, and 3 months postpartum, and TGF-β1, TGF-β2, and IgA levels were measured.Results: No adverse effects were observed in the probiotic group, according to the self-recorded diary during the study period. Milk IgA decreased with increasing postpartum months in both groups. In contrast, TGF- β1 and β2 were not affected by lactation periods, and showed different patterns over time between the two groups. TGF-β1, TGF-β1, and IgA levels were significantly correlated at baseline (respectively p < 0.05). However, the correlation between TGF-β1 and IgA became non-significant by the end of the intervention (p = 0.063).Conclusion: Altogether, probiotic supplementation was tolerated with respect to no dropout and 91.5% adherence. Although probiotic supplementation might affect human milk TGF-β levels, a positive effect of probiotic supplementation was not entirely supported. Future placebo-controlled studies are needed to further support the efficacy and safety of probiotic supplementation.Clinical Trial Registration: www.umin.ac.jp/ctr/, identifier: UMIN000036059.

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Section: Discussionmentioning

confidence: 86%

Effects of Probiotic Supplementation on TGF-β1, TGF-β2, and IgA Levels in the Milk of Japanese Women: An Open-Label Pilot Study

et al. 2019

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“…Several epidemiological studies have reported that IBD mothers receiving therapy should not be discouraged from nursing their children and nursing may even provide a protective effect against disease flare in the postpartum year, 6,22 whereas other studies have not found such associations. 29,30 Breastfeeding is known to provide significant health benefits to infants, including the transmission of protective antibodies, 31 cytokines, 15,32 immunoreactive biochemicals and leukocytes. 20,33 Unlike most mammals, human breast milk antibodies that are transferred from mother to infant do not enter the child's circulation in large amounts.…”

Section: Discussionmentioning

confidence: 99%

The Profile of Human Milk Metabolome, Cytokines, and Antibodies in Inflammatory Bowel Diseases Versus Healthy Mothers, and Potential Impact on the Newborn

Meng

Dunsmore

Koleva

et al. 2018

Journal of Crohn's and Colitis

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Background and Aims: For women with inflammatory bowel disease [IBD], it is not very well known how IBD or IBD treatment affects their breast milk components. We aimed to investigate whether breast milk composition differs in healthy control [HC] versus IBD mothers in terms of antibodies, cytokines, and metabolite,s to identify potential impact of IBD breast milk on neonatal immune system. Methods: Breast milk specimens from HC [n = 17] and IBD [n = 31 for Crohn's disease [CD]; and n = 41 for ulcerative colitis [UC]; were collected at 3 and 6 months postpartum [PP3] and [PP6], respectively. Faecal samples were also collected. Cytokines and immunoglobulins [IgA/IgG/IgE] were analysed by multiplex Meso Scale Discovery [MSD] and commercial kits. Moreover, breast milk metabolites were analysed by 1 H nuclear magnetic resonance [NMR]. Results: We found that breast milk from IBD mothers showed significantly lower levels of IgA, sugar metabolite [lactose], and 2-aminobutyrate. In contrast, we observed that breast milk from mothers with IBD had increased levels of pro-inflammatory cytokines and higher energy metabolites [lactate and succinate] than milk from healthy mothers. In addition, we noticed that the type of treatment [5-aminosalicylic acid versus biologics] influenced the milk cytokines and metabolites profile. Conclusions: The reduction in immunoprotective components of IBD breast milk such as sIgA and lactose theoretically may modulate the potential protective effects of breastfeeding. On the other hand, presence of higher levels of pro-inflammatory cytokines, lactate, and succinate may predispose the offspring to an inflammatory condition or impact on the gut microbiome. Better understanding of the role of succinate in infants and its potential effects on microbiome or mucosal immunity merits further investigations.

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“…(101). Interestingly, other studies have shown that milk from healthy black women may contain higher levels of IL-1β than from white women even when controlled for BMI (102), which strengthens the hypothesis that increased inflammation within the breast of black women compared with white women may be linked to the higher rates of early onset breast cancer in black women (103). Therefore, potential strategies to reduce racial disparities in breast cancer risk could be through interventions such as short courses of anti-inflammatory agents (102).…”

Section: Serum Cytokine Profile In Breast Cancer Patients Of Different Racial/ethnic Backgroundsmentioning

confidence: 98%

The Contribution of Race to Breast Tumor Microenvironment Composition and Disease Progression

et al. 2020

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Breast cancer is the second most commonly diagnosed cancer in American women following skin cancer. Despite overall decrease in breast cancer mortality due to advances in treatment and earlier screening, black patients continue to have 40% higher risk of breast cancer related death compared to white patients. This disparity in outcome persists even when controlled for access to care and stage at presentation and has been attributed to differences in tumor subtypes or gene expression profiles. There is emerging evidence that the tumor microenvironment (TME) may contribute to the racial disparities in outcome as well. Here, we provide a comprehensive review of current literature available regarding race-dependent differences in the TME. Notably, black patients tend to have a higher density of pro-tumorigenic immune cells (e.g., M2 macrophages, regulatory T cells) and microvasculature. Although immune cells are classically thought to be anti-tumorigenic, increase in M2 macrophages and angiogenesis may lead to a paradoxical increase in metastasis by forming doorways of tumor cell intravasation called tumor microenvironment of metastasis (TMEM). Furthermore, black patients also have higher serum levels of inflammatory cytokines, which provide a positive feedback loop in creating a pro-metastatic TME. Lastly, we propose that the higher density of immune cells and angiogenesis observed in the TME of black patients may be a result of evolutionary selection for a more robust immune response in patients of African geographic ancestry. Better understanding of race-dependent differences in the TME will aid in overcoming the racial disparity in breast cancer mortality.

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Pro-inflammatory cytokines and growth factors in human milk: an exploratory analysis of racial differences to inform breast cancer etiology

Abstract: This exploratory study demonstrated the feasibility of measuring pro-inflammatory cytokines, adipokines, and angiogenesis factors in human milk, and revealed higher levels of some pro-inflammatory factors, as well as increased leptin levels, among Black as compared with White women.

Cited by 17 publications

References 41 publications

Effects of Probiotic Supplementation on TGF-β1, TGF-β2, and IgA Levels in the Milk of Japanese Women: An Open-Label Pilot Study

Effects of Probiotic Supplementation on TGF-β1, TGF-β2, and IgA Levels in the Milk of Japanese Women: An Open-Label Pilot Study

The Profile of Human Milk Metabolome, Cytokines, and Antibodies in Inflammatory Bowel Diseases Versus Healthy Mothers, and Potential Impact on the Newborn

The Contribution of Race to Breast Tumor Microenvironment Composition and Disease Progression

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