The human gut is a composite anaerobic environment with a large, diverse and 
dynamic enteric microbiota, represented by more than 100 trillion 
microorganisms, including at least 1000 distinct species. The discovery that a 
different microbial composition can influence behavior and cognition, and in 
turn the nervous system can indirectly influence enteric microbiota composition, 
has significantly contributed to establish the well-accepted concept of 
gut-brain axis. This hypothesis is supported by several evidence showing mutual 
mechanisms, which involve the vague nerve, the immune system, the 
hypothalamic-pituitaryadrenal (HPA) axis modulation and the bacteria-derived 
metabolites. Many studies have focused on delineating a role for this axis in 
health and disease, ranging from stress-related disorders such as depression, 
anxiety and irritable bowel syndrome (IBS) to neurodevelopmental disorders, such 
as autism, and to neurodegenerative diseases, such as Parkinson Disease, 
Alzheimer's Disease etc. Based on this background, and considering the relevance 
of alteration of the symbiotic state between host and microbiota, this review 
focuses on the role and the involvement of bioactive lipids, such as the 
N-acylethanolamine (NAE) family whose main members are 
N-arachidonoylethanolamine (AEA), palmitoylethanolamide (PEA) and 
oleoilethanolamide (OEA), and short chain fatty acids (SCFAs), such as butyrate, 
belonging to a large group of bioactive lipids able to modulate peripheral and 
central pathologic processes. Their effective role has been studied in 
inflammation, acute and chronic pain, obesity and central nervous system 
diseases. A possible correlation has been shown between these lipids and gut 
microbiota through different mechanisms. Indeed, systemic administration of 
specific bacteria can reduce abdominal pain through the involvement of 
cannabinoid receptor 1 in the rat; on the other hand, PEA reduces inflammation 
markers in a murine model of inflammatory bowel disease (IBD), and butyrate, 
producted by gut microbiota, is effective in reducing inflammation and pain in 
irritable bowel syndrome and IBD animal models. In this review, we underline the 
relationship among inflammation, pain, microbiota and the different lipids, 
focusing on a possible involvement of NAEs and SCFAs in the gut-brain axis and 
their role in the central nervous system diseases.