ABSTRACT
Palmitoylethanolamide (PEA) is an endocannabinoid-like bioactive lipid mediator belonging to the family of N-acylethanolamines, most abundantly found in peanuts and egg yolk. When the gastrointestinal (GI) effects of PEA are discussed, it must be pointed out that it affects intestinal motility but also modulates gut microbiota. This is due to anti-inflammatory, antioxidant, analgesic, antimicrobial, and immunomodulatory features. Additionally, PEA has shown beneficial effects in several GI diseases, particularly irritable bowel syndrome and inflammatory bowel diseases, as various studies have shown, and it is important to emphasize its relative lack of toxicity, even at high dosages. Unfortunately, there is not enough endogenous PEA to treat disturbed gut homeostasis, even though it is produced in the GI tract in response to inflammatory stimuli, so exogenous intake is mandatory to achieve homeostasis. Intake of PEA could be through animal and/or vegetable food, but bearing in mind that a high dosage is needed to achieve a therapeutic effect, it must be compensated through dietary supplements. There are still open questions pending to be answered, so further studies investigating PEA's effects and mechanisms of action, especially in humans, are crucial to implementing PEA in everyday clinical practice.
ABSTRACT
INTRODUCTION: Metabolic Dysfunction-associated Liver Disease (MASLD) represents a spectrum of conditions from simple fat accumulation to non-alcoholic steatohepatitis. The possible role of the intestinal microbiome on MASLD development has been in focus. Our study aimed to examine the effects of synbiotics on the liver steatosis, inflammation, and stool microbiome. METHODS: A double-blind, placebo-controlled study was conducted involving 84 MASLD patients, defined by an elastometric attenuation coefficient (ATT) greater than 0.63 dB/cm/MHz with an alanine aminotransferase level above 40 U/L for men and 35 U/L for women. The patients were divided into an intervention group treated with a synbiotic with 64x109 CFU of Lactobacillus and Bifidobacterium and 6.4g of inulin and a control group treated with a placebo. RESULTS: Using synbiotics for 12 weeks significantly decreased liver steatosis (ΔATT -0.006±0.023 vs -0.016±0.021 dB/cm/MHz, p=0.046). The group of patients treated with synbiotics showed a significant decrease in the level of high-sensitive C-reactive protein (Δhs-CRP 0 vs -0.7 mg/L, p≤0.001). Synbiotics enriched the microbiome of patients in the intervention group with the genera Lactobacillus, Bifidobacterium, Faecalibacterium, and Streptococcus, by 81%, 55%, 51%, and 40%, respectively, with a reduction of Ruminococcus and Enterobacterium by 35% and 40%. Synbiotic treatment significantly shortened the gut transition time (ΔGTT -5h vs. -10h, p=0.031). CONCLUSION: Synbiotics could be an effective and safe option that could have place in MASLD treatment.
