Excessive Intake of Longan Arillus Alters Gut Homeostasis and Aggravates Colitis in Mice

Background: Longan is the fruit of Dimocarpus longan Lour. and the longan arillus has been used in traditional Chinese medicine for thousands of years possessing various health benefits. However, the excessive intake of longan is found in daily life to cause “ shanghuo ” syndrome. Shanghuo has been linked to increased disease susceptibility. The present study thus aimed to investigate the toxicological outcomes after excess longan treatment. Methods: Longan extract at a normal dosage of 4 g/kg and two excess dosages of 8 and 16 g/kg was orally administered to normal C57BL/6J mice for 2 weeks. Another set of study used C57BL/6J mice with dextran sulfate sodium (DSS)-induced colitis by giving mice drinking water containing 3.5% DSS for 5 consecutive days. Mouse feces were collected at the end of experiments for microbial analysis by 16S rRNA sequencing. After mice were sacrificed, colonic contents were collected for measurement of short-chain fatty acid (SCFA) contents. Colon tissue was used for histopathological observation after H&E staining, detection of ZO-1 protein expression by western blot, analysis of TNF-α and IL-6 gene expression, and detection of apoptotic cells by TUNEL assay. Serum was collected for analysis of LPS, TNF-α and IL-6 by ELISA method. Results: In normal mice, repeated longan intake at excess doses, but not the normal dose, increased infiltration of inflammatory cells, elevated serum levels of TNF-α and IL-6 and reduced production of SCFAs. In DSS-induced colitic mice, longan intake at 4 g/kg did not promoted colitis in mice, while excess longan (8 or 16 g/kg) enhanced colitis in mice, showing increased inflammation (shorter colon length, upregulated IL-1β and TNF-α ), more serious histological abnormalities, increased gut permeability (decreased ZO-1 protein expression), and increased epithelia injury (increased TUNEL-positive cells) when compared to DSS alone. Excess longan induced a significant reduction of microbial diversity in colitic mice, accompanied with aggravated alterations of DSS-associated bacteria including the increase of Proteobacteria phylum and genera of Bacteroides , Akkermansia , Turicibacter and Escherchia-Shigella , and the decrease of norank_f__Muribaculaceae . The changed microbial compositions were accompanied with decreased SCFAs when longan was supplemented with DSS. The altered microbial communities and SCFAs were tightly correlated with aggravated colon injury in mice. Conclusions: Excess longan intake disturbs gut homeostasis and aggravates colitis via promoting inflammation and altering gut microbe compositions and associated metabolism in mice. Our findings warrant rational longan arillus consumption as a dietary supplement among general population and suggest contraindications such as inflammatory bowel disease of using longan as an herbal medicine.