Microbiome–Gut Dissociation in the Neonate: Autism-Related Developmental Brain Disease and the Origin of the Placebo Effect

IF 0.9 Q4 GASTROENTEROLOGY & HEPATOLOGY
David Smith, S. Jheeta, Hannya V. Fuentes, B. Street, Miryam Palacios-Pérez
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引用次数: 1

Abstract

While the importance of the intestinal microbiome has been realised for a number of years, the significance of the phrase microbiota–gut–brain axis is only just beginning to be fully appreciated. Our recent work has focused on the microbiome as if it were a single entity, modifying the expression of the genetic inheritance of the individual by the generation of interkingdom signalling molecules, semiochemicals, such as dopamine. In our view, the purpose of the microbiome is to convey information about the microbial environment of the mother so as to calibrate the immune system of the new-born, giving it the ability to distinguish harmful pathogens from the harmless antigens of pollen, for example, or to help distinguish self from non-self. In turn, this requires the partition of nutrition between the adult and its microbiome to ensure that both entities remain viable until the process of reproduction. Accordingly, the failure of a degraded microbiome to interact with the developing gut of the neonate leads to failure of this partition in the adult: to low faecal energy excretion, excessive fat storage, and concomitant problems with the immune system. Similarly, a weakened gut–brain axis distorts interoceptive input to the brain, increasing the risk of psychiatric diseases such as autism. These effects account for David Barker’s 1990 suggestion of “the fetal and infant origins of adult disease”, including schizophrenia, and David Strachan’s 1989 observation of childhood immune system diseases, such as hay fever and asthma. The industrialisation of modern life is increasing the intensity and scale of these physical and psychiatric diseases and it seems likely that subclinical heavy metal poisoning of the microbiome contributes to these problems. Finally, the recent observation of Harald Brüssow, that reported intestinal bacterial composition does not adequately reflect the patterns of disease, would be accounted for if microbial eukaryotes were the key determinant of microbiome effectiveness. In this view, the relative success of “probiotic” bacteria is due to their temporary immune system activation of the gut–brain axis, in turn suggesting a potential mechanism for the placebo effect.
新生儿微生物群-肠道分离:自闭症相关的发育性脑疾病和安慰剂效应的起源
尽管肠道微生物组的重要性已经认识到很多年了,但微生物群-肠-脑轴这一短语的重要性才刚刚开始被充分认识。我们最近的工作集中在微生物组上,就好像它是一个单一的实体,通过产生界间信号分子、信息化学物质(如多巴胺)来改变个体遗传的表达。在我们看来,微生物组的目的是传递有关母亲微生物环境的信息,从而校准新生儿的免疫系统,使其能够区分有害病原体和花粉的无害抗原,或者帮助区分自我和非自我。反过来,这需要在成虫及其微生物组之间分配营养,以确保这两个实体在繁殖过程中都保持活力。因此,降解的微生物组未能与新生儿发育中的肠道相互作用,导致成年人的这种分配失败:粪便能量排泄低、脂肪储存过多,以及随之而来的免疫系统问题。同样,肠脑轴减弱会扭曲大脑的内感受输入,增加患自闭症等精神疾病的风险。这些影响解释了David Barker 1990年提出的“成人疾病的胎儿和婴儿起源”,包括精神分裂症,以及David Strachan 1989年对儿童免疫系统疾病的观察,如花粉热和哮喘。现代生活的工业化正在增加这些身体和精神疾病的强度和规模,微生物组的亚临床重金属中毒似乎很可能导致了这些问题。最后,如果微生物真核生物是微生物组有效性的关键决定因素,则可以解释Harald Brüssow最近的观察结果,即报告的肠道细菌组成不能充分反映疾病模式。在这种观点中,“益生菌”的相对成功是由于它们的肠-脑轴的暂时免疫系统激活,这反过来又表明了安慰剂效应的潜在机制。
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