PO.IM02.03 · 免疫学
益生元纤维补充可减轻母体肥胖对子代肠道微生物组和乳腺肿瘤发生的影响
Prebiotic fiber supplementation mitigates the effects of maternal obesity on offspring's gut microbiome and mammary tumorigenesis
该海报暂无可下载的资料
AACR 官方页面
作者与单位 Authors & Affiliations
摘要 Abstract
中文摘要
母体肥胖的患病率在连续数十年间逐渐上升，目前美国超过50%的孕前女性被归类为超重或肥胖。母体肥胖对众多妊娠结局产生有害影响，并给子代带来持久的负面健康后果，包括提高雌性子代对乳腺癌的易感性和死亡率。由于肠道微生物组促成肥胖及其不良影响，并影响乳腺癌发生，我们在此研究了饮食诱导肥胖的C57BL/6母鼠所生子代（OB子代）中以粪便短链脂肪酸（SCFA）水平降低为特征的肠道菌群失调，是否与其相比对照子代更高的E0771乳腺肿瘤负荷有关。将OB子代的粪便微生物移植（FMT）到对照子代宿主中增加了E0771乳腺肿瘤负荷，提示肠道菌群失调与OB子代乳腺肿瘤发生增加之间存在因果关系。此外，接受来自OB子代供体FMT的对照子代，其肠道派尔集合淋巴结中CD4+ T细胞、CD8+ T细胞和Foxp3+调节性T细胞以及肿瘤中CD8+ T细胞的SCFA受体FFAR2水平，显著低于接受来自对照子代供体FMT者。为确定OB子代乳腺肿瘤发生增加是否可通过膳食纤维增加粪便SCFA产生而逆转，我们采用了MMTV-PyMT乳腺肿瘤模型，其中乳腺肿瘤在4月龄时"自发"形成。我们的结果表明，MMTV-PyMT OB子代相比对照表现出显著增加的乳腺肿瘤负荷。通过饮水给子代补充部分水解瓜尔胶（PHGG）这一益生元纤维，相比接受麦芽糊精（MDX）对照的OB子代，表现出显著更低的乳腺肿瘤发生和更高的粪便SCFA丙酸水平。相比之下，接受PHGG的对照子代未表现出乳腺肿瘤发生的变化，尽管PHGG补充增加了它们的粪便丁酸水平。这些结果提示OB子代乳腺肿瘤发生的增加与其肠道菌群失调相关。此外，成年OB子代摄入益生元纤维PHGG可逆转母体肥胖对其肠道微生物组和乳腺肿瘤发生的不良影响。
查看英文原文 English abstract
The prevalence of maternal obesity has gradually increased over successive decades, with over 50% of pre-pregnant women in the United States at present time classified as overweight or obese. Maternal obesity exerts deleterious effects on numerous pregnancy outcomes and imparts enduring negative health consequences on offspring, including elevating female offspring's susceptibility to and mortality from breast cancer. Since the gut microbiome contributes to obesity and its adverse effects, and influences breast carcinogenesis, we investigated here whether gut dysbiosis, characterized by reduced fecal short-chain fatty acid (SCFA) levels, in mouse offspring born to diet-induced obese C57BL/6 dams (OB offspring) contributed to their higher E0771 mammary tumor burden, compared with control offspring. Fecal microbiota transplant (FMT) from OB offspring increased E0771 mammary tumor burden in control offspring host, suggesting a causality between gut dysbiosis and increased mammary tumorigenesis in OB offspring. Further, levels of SCFA receptor FFAR2 in CD4+ T cells, CD8+ T cells and Foxp3+ regulatory T cells in Peyer's patches in gut and in CD8+ T cells in tumors were significantly lower in control offspring receiving FMT from OB offspring donor than from control offspring donor. To determine if increased mammary tumorigenesis in OB offspring can be reversed by increasing fecal SCFA production by dietary fiber, we employed the MMTV-PyMT mammary tumor model, in which mammary tumors develop “spontaneously” by 4 months of age. Our results indicated that MMTV-PyMT OB offspring exhibited significantly increased mammary tumor burden compared with controls. Supplementing offspring via drinking water with partially hydrolyzed guar gum (PHGG), a prebiotic fiber, exhibited significantly lower mammary tumorigenesis and higher fecal levels of SCFA propionic acid than OB offspring receiving maltodextrin (MDX) control. In contrast, control offspring receiving PHGG did not show changes in mammary tumorigenesis, although PHGG supplementation increased their fecal butyric acid levels. These results suggest that increased mammary tumorigenesis in OB offspring are linked to their gut dysbiosis. In addition, prebiotic
fiber PHGG, consumed by adult OB offspring, reverses adverse effects of maternal obesity on both their gut microbiome and mammary tumorigenesis.
利益披露 Disclosure
S. Yadav, None..
F. Andrade, None..
M. Ozgul Onal, None..
S. Shirk, None..
S. Kenanogly, None..
L. Hilakivi-Clarke, None.