Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland; APC Microbiome Ireland, University College Cork, Cork, Ireland.
Medical and Scientific Affairs, Reckitt | Mead Johnson Nutrition Institute, Nijmegen, the Netherlands.
Neuropharmacology. 2022 Jun 1;210:109026. doi: 10.1016/j.neuropharm.2022.109026. Epub 2022 Mar 10.
Nutritional approaches have emerged over the past number of years as suitable interventions to ameliorate the enduring effects of early life stress. Maternal separation (MS) is a rodent model of early life stress which induces widespread changes across the microbiota-gut-brain axis. Milk fat globule membrane (MFGM) is a neuroactive membrane structure that surrounds milk fat globules in breast milk and has been shown to have positive health effects in infants, yet mechanisms behind this are not fully known. Here, we investigated the effects of MFGM supplementation from birth on a variety of gut-brain signalling pathways in MS and non-separated control animals across the lifespan. Specifically, visceral sensitivity as well as spatial and recognition memory were assessed in adulthood, while gut barrier permeability, enteric nervous system (ENS) and glial network structure were evaluated in both early life and adulthood. MS resulted in visceral hypersensitivity, which was ameliorated to a greater extent by supplementation with MFGM from birth. Modest effects of both MS and dietary supplementation were noted on spatial memory. No effects of MS were observed on enteric neuronal or glial networks in early life or adulthood, however an increase in the immunoreactivity of βIII-tubulin in adult colonic myenteric ganglia was noted in the MFGM intervention non-separated group. In conclusion, dietary supplementation with MFGM from birth is sufficient to block MS-induced visceral hypersensitivity, highlighting its potential value in visceral pain-associated disorders, but future studies are required to fully elucidate the mechanistic role of this supplementation on MS-induced visceral pain.
在过去的几年中,营养方法已成为改善早期生活压力持久影响的合适干预措施。母体分离(MS)是一种早期生活压力的啮齿动物模型,它会导致微生物群-肠道-大脑轴的广泛变化。乳脂肪球膜(MFGM)是一种神经活性膜结构,围绕着母乳中的乳脂肪球,已被证明对婴儿有积极的健康影响,但背后的机制尚不完全清楚。在这里,我们研究了从出生开始补充 MFGM 对 MS 和非分离对照组动物在整个生命周期中各种肠道-大脑信号通路的影响。具体来说,在成年期评估内脏敏感性以及空间和识别记忆,而在成年期和成年期评估肠道屏障通透性、肠神经系统(ENS)和神经胶质网络结构。MS 导致内脏敏感性增加,从出生开始补充 MFGM 可更大程度地缓解这种情况。MS 和饮食补充都对空间记忆有适度的影响。MS 对早期和成年期的肠神经元或神经胶质网络没有影响,但在 MFGM 干预非分离组中,成年结肠肌间神经节中 βIII-微管蛋白的免疫反应性增加。总之,从出生开始补充 MFGM 足以阻止 MS 引起的内脏敏感性增加,这突出了其在与内脏疼痛相关的疾病中的潜在价值,但需要进一步的研究来充分阐明这种补充对 MS 引起的内脏疼痛的机制作用。