Devaux Christian A, Raoult Didier
IRD, APHM, MEPHI, IHU-Méditerranée Infection, Aix-Marseille University, Marseille, France.
Centre National de la Recherche Scientifique, Marseille, France.
Front Microbiol. 2018 Jun 26;9:1379. doi: 10.3389/fmicb.2018.01379. eCollection 2018.
If the transmission of biological information from one generation to the next is based on DNA, most heritable phenotypic traits such as chronic metabolic diseases, are not linked to genetic variation in DNA sequences. Non-genetic heritability might have several causes including epigenetic, parental effect, adaptive social learning, and influence of the ecological environment. Distinguishing among these causes is crucial to resolve major phenotypic enigmas. Strong evidence indicates that changes in DNA expression through various epigenetic mechanisms can be linked to parent-offspring resemblance in terms of sensitivity to metabolic diseases. Among non-genetic heritable traits, early nutrition could account for a long term deviant programming of genes expression responsible for metabolic diseases in adulthood. Nutrition could shape an inadequate gut microbiota (dysbiosis), triggering epigenetic deregulation of transcription which can be observed in chronic metabolic diseases. We review herein the evidence that dysbiosis might be a major cause of heritable epigenetic patterns found to be associated with metabolic diseases. By taking into account the recent advances on the gut microbiome, we have aggregated together different observations supporting the hypothesis that the gut microbiota could promote the molecular crosstalk between bacteria and surrounding host cells which controls the pathological epigenetic signature. We introduce for the first time the concept of "microbiological memory" as the main regulator of the epigenetic signatures, thereby indicating that different causes of non-genetic heritability can interact in complex pathways to produce inheritance.
如果生物信息从一代向下一代的传递是基于DNA，那么大多数可遗传的表型特征，如慢性代谢疾病，并不与DNA序列中的遗传变异相关。非遗传遗传性可能有多种原因，包括表观遗传、亲代效应、适应性社会学习以及生态环境的影响。区分这些原因对于解决主要的表型谜团至关重要。有力证据表明，通过各种表观遗传机制导致的DNA表达变化，在对代谢疾病的易感性方面可能与亲子相似性有关。在非遗传可遗传性状中，早期营养可能导致成年后负责代谢疾病的基因表达出现长期异常编程。营养可能塑造出不适当的肠道微生物群（生态失调），引发转录的表观遗传失调，这在慢性代谢疾病中可以观察到。我们在此回顾证据，表明生态失调可能是与代谢疾病相关的可遗传表观遗传模式的主要原因。通过考虑肠道微生物组的最新进展，我们汇总了不同的观察结果，支持肠道微生物群可能促进细菌与周围宿主细胞之间的分子串扰这一假说，而这种串扰控制着病理表观遗传特征。我们首次引入“微生物记忆”的概念，将其作为表观遗传特征的主要调节因子，从而表明非遗传遗传性的不同原因可以在复杂的途径中相互作用以产生遗传。
