Stem Cell Epigenetics 2015; 2: e863. doi: 10.14800/sce.863; © 2015 by Omotuyi, et al. http://www.smartscitech.com/index.php/sce Page 1 of 2 Hypothetical epigenetic fingerprint in Nutritional-Neural-microbiota connection Olaposi I. Omotuyi 1,2 1 Department of pharmacology and Therapeutic innovation, Graduate School of Biomedical Sciences, Nagasaki University, Japan 2 Center for Bio-computing, Adekunle Ajasin University, Akungba-Akoko. Ondo State, Nigeria Correspondence: Olaposi Omotuyi E-mail: omotuyi@nagasaki-u.ac.jp Received: June 05, 2015 Published online: June 23, 2015 To cite this article: Omotuyi, et al. Hypothetical epigenetic fingerprint in Nutritional-Neural-microbiota connection. Stem Cell Epigenet 2015; 2: e863. doi: 10.14800/sce.863. A medical case was reported by Neha and Colleen of a 32-year-old female who had received Fecal microbial transplantation (FMT) as a consequent of recurring Clostridium difficile infection (CDI). Following this procedure, the recipient began to experience significant weight comorbid with constipation and dyspepsia episodes. The weight gain is unamendable by strict protein diet and exercise regimen, thus, leading the authors to hypothesize nutritional-neural-microbiota connection [1] . This hypothesis is further reinforced as animals were transformed into obese phenotypes following fecal transplant from obese human [2] . To begin to make the connection, we have to dive a bit into the current body of knowledge about the molecular basis of obesity. Alteration in effective circulating leptin/ghrelin balance and their cognate receptors is one of the leading causes of obesity. One of the major sites of leptin and gherlin receptors expression is the hypothalamus, making obesity arguably a brain disease. Over-expression of leptin receptor is associated with leanness, while the converse is true for ghrelin receptor over-expression as well reported during pregnancy [3] and provides a scientific basis for obese phenotypes induced in animal model when treated with leptin receptor antagonists [4] . Obesity episode in the animals was preceded by increased food consumption, similar to what is expected when animals were treated with appetite stimulants such as gherkin, orexin and neuropeptide-Y, succinctly making the connection between food/energy intake (nutritional) and the neural circuitry. How does the nutritional-neural axis link up with the microbiota and what is the epigenetic connection? These two questions represent the core of this write-up and since our knowledge of this interaction is premature, we must necessarily fall back to our current understanding of host-pathogen interaction and draw valuable epigenetic lessons from this relationship. Microbes have at least two important epigenetic modifying factors in their arsenal to alter gene expression; first, they have surface signals, which rely on coupling to receptor on host cells for onward intracellular transmission of epigenetic information like classical paracrine factors. Then, they can produce secondary metabolites, which behave like classical endocrine factors, crossing through physical barriers and dispersing in serum and reaching distant targets like the brain. For instance, Campylobacter rectus and Helicobacter pylori infection cause insulin-like growth factor (igf2) [5] and Runt-related transcription factor 3 (runx3) [6] promotor hypermethylation respectively. A few metabolites such as cysteine, propionate, sulforaphane and spermidine have been characterized as epigenetic modulators and of note is the p21 expression modulation by short chain fatty acids via Histone-deacetylase 1 inhibition [7] . COMMENTARY