Lactobacillus acidophilus regulates abnormal serotonin availability in experimental ulcerative colitis

Ulcerative colitis, which is a type of inflammatory bowel disease, is intestinal inflammation that occurs with the interaction of environmental and genetic factors. In this condition, which is characterized by inflammation of the mucosal layer of the intestine, clinical findings such as fluid and electrolyte loss, ulceration and bleeding are seen [1].

To date, anti-inflammatory drugs and immunosuppressants have been used in the treatment of ulcerative colitis to alleviate the symptoms that are effective in the early stages of colitis [2]. Since there is no specific treatment for ulcerative colitis, efforts have been made in recent years to understand the pathogenesis of ulcerative colitis and to develop new treatment methods [3,4]. However, many side effects caused by therapeutic methods have also been reported in studies [1]. New treatment modalities targeting the mechanisms of specific diseases have the potential to provide more effective and reliable treatment for inflammatory bowel diseases. One of the most interesting areas of inflammatory bowel disease research is the use of probiotics therapy. Probiotics, known as microbial supplements, regulate the intestinal microbial balance and strengthen the intestinal barrier function [5]. There are many studies in the literature showing that the intestinal flora has an important role in intestinal inflammation [6,7]. Studies have shown that ulcerative colitis can be treated by increasing the number of probiotics in the intestinal flora [[8], [9], [10]]. Consequently, there has been increasing interest in investigating the beneficial roles of probiotics in controlling and curing diseases. There are also studies showing that the use of multiple probiotics is effective in the treatment of intestinal diseases and may be a promising alternative treatment method [2,[11], [12], [13]]. However, the literature on the protective effects of probiotics in inflammatory bowel diseases is insufficient and the mechanism is still unclear. Commensal Lactobacillus species are dominant in the intestinal microflora and these species are known to play a protective role against inflammatory bowel diseases [14]. Lactobacillus acidophilus (L. acidophilus) is one of the most widely used species of the genus Lactobacillus, known to have beneficial effects on the microbiota of the gastrointestinal tract [15,16]. L. acidophilus is known to reduce the risk of blood cholesterol, lactose, constipation and diarrhea. This bacterial strain is also considered an antagonist against intestinal pathogens and can survive for long periods in complex gastrointestinal ecosystems [17]. The clinical use of L. acidophilus for therapeutic purposes has been reported [18]. Although studies have shown that L. acidophilus can improve clinical symptoms in patients with inflammatory bowel disease, the underlying mechanism is not clear. It has previously been shown that treatment with L. acidophilus can effectively ameliorate experimental ulcerative colitis in mice [14]. Ulcerative lesions in the colon mucosa, immune cell infiltration, and changes in the presence of serotonin (5-HT) are observed in ulcerative colitis [19]. Previous studies have reported that 5-HT can regulate the gastrointestinal system by both initiating secretory, vagal, and nociceptive reflexes and activating immune cells [20]. 5-HT is mostly secreted by the enterochromaffin cells in the intestine and acts by binding to its receptors [1]. Changes in the number of enterochromaffin cells and 5-HT protein content have been reported to be associated with inflammatory bowel diseases, as during intestinal inflammation, the number of enterochromaffin cells often increases, resulting in higher levels of 5-HT released [21]. Therefore, there can be said to be a close relationship between various gastrointestinal diseases and serotonin signal in terms of maintaining intestinal homeostasis.

The microbiota is located throughout the gastrointestinal tract and can physiologically affect the host in a variety of ways. In one study, lower mucosal 5-HT protein content and a lower number of enterochromaffin cells were detected both in mice with no innate microbiota and in mice that received antibiotic treatment compared to normal mice. The results of that study suggested, that the microbial ecosystem changes the levels of microbial metabolites in the intestinal lumen and affects the levels of 5-HT in the circulation, which is likely to exert a regulatory effect on 5-HT biosynthesis in enterochromaffin cells [22].

It is known that there is an altered gut microbiome characterized by a reduction in microbial diversity in inflammatory bowel diseases, including ulcerative colitis [23]. Most bacteria are capable of producing 5-HT, and microbial 5-HT metabolism is potentially altered in inflammatory bowel disease patients. Previous studies have shown that the number of species belonging to the Lactobacillaceae family is decreased in patients with ulcerative colitis but the mechanism remains unclear [24,25]. Recent reports have indicated that abnormalities in serotonergic signaling systems are involved in the development of irritable bowel syndrome [26,27]. It is known that 5-HT plays an important role in the pathogenesis of ulcerative colitis, but the effect of L. acidophilus applied for treatment after ulcerative colitis on 5-HT level has not been investigated. In this context, the aim of this study was to investigate the effect of L. acidophilus on 5-HT expression induced by acetic acid in a colitis model in rats and to compare the protective and therapeutic effects of L. acidophilus on colitis.

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