1. Introduction
Rich in nutrients, yak yogurt is a naturally fermented dish often found in the minority areas of the Qinghai–Tibet Plateau [
1]. Yak yogurt offers several physiological benefits, including decreasing cholesterol, boosting the immune system, and acting as an antioxidant. The taste and quality of yak yogurt differ greatly from regular fermented milk due to the distinct natural fermentation environment of the Qinghai–Tibet Plateau, the use of yak milk and special fermentation vessels, and the unique fermentation microorganisms of the Tibetan people [
2]. The
Lactiplantibacillus plantatum HFY11 used in this study was a strain of lactic acid bacteria that can be used for food after the isolation and identification of yak yogurt microorganisms in the Hongyuan area of the Qinghai–Tibet Plateau in Sichuan Province, China.
Colitis is an inflammatory intestinal disease, mainly involving inflammation and damage to the colon (large intestine) mucosa. The inflammation and damage to the mucosa interfere with the normal digestion and absorption of food, resulting in discomfort and malnutrition. At the same time, patients with colitis often have problems such as loss of appetite and indigestion, leading to weight loss [
3]. If colitis is not effectively treated or controlled, the inflammation may further expand and lead to serious complications, such as intestinal obstruction, bleeding, and perforation. This increases the health risks and the need for medical intervention [
4]. In addition, patients with colitis may often experience abdominal pain, abdominal discomfort, and colic. Colitis has a multifaceted impact on the human body, which is not only limited to digestive system problems, but may also involve malnutrition, weight changes, pain, and discomfort. Therefore, timely diagnosis, active treatment, and disease management are essential for patients with colitis [
5]. Oxazolone can induce a T-cell-mediated immune response. The cell-mediated type 2 (Th2) immune response and interleukin-4 (IL-4) and IL-5 production increase significantly, accompanied by weight loss, diarrhea, ulcers, and a decreased number of colorectal epithelial cells [
6]. The oxazolone-induced ulcerative colitis model is frequently used to identify the physiological action of medications and functional foods in colitis in humans because both show similar symptoms.
Probiotics have a certain impact and potential benefits on colitis; they can help restore the balance of intestinal microbiota, enhance the integrity of the intestinal mucosal barrier, and regulate the immune system [
7]. Probiotics can reduce the inflammatory response and symptoms in patients with colitis by enhancing the composition and function of the intestinal microbiota, inhibiting the growth of pathogenic bacteria, and increasing the number of beneficial bacteria [
8]. They may enhance the quality of life of patients and aid in the relief of digestive system issues such as constipation, diarrhea, and stomach discomfort [
9,
10,
11]. In addition, probiotics can also enhance the integrity of the intestinal mucosal barrier and reduce the penetration of harmful substances and bacteria, and thus reduce the degree of inflammation. They can also regulate the immune response, reduce the release of inflammatory factors, and promote the resolution of inflammation, thus helping to control the progression of colitis [
12].
Lactobacillus with good physiological activity can be developed and used as a probiotic. Our group investigated the intestinal physiological activity of lactic acid bacteria found in yak yogurt from the Qinghai–Tibet Plateau. The findings demonstrate that lactic acid bacteria separated from yak yogurt had an antioxidant and constipation-relieving effect. Thus, this study was performed to investigate the impact of an L. plantarum HFY11 (LP-HFY11) strain isolated from yak yogurt on oxazolone-induced colitis. The findings of this study might give us a theoretical foundation for the development and use of LP-HFY11 in the future.
4. Discussion
Colitis can cause weight loss, diarrhea, and other symptoms. DAI is a grading system for determining the severity of colitis based on body weight, stool parameters, and fecal blood [
16]. According to the DAI index, we discovered that LP-HFY11 might alleviate the symptoms of oxazolone-induced colitis, with the impact becoming more significant when increasing the concentration of LP-HFY11. In addition, the colon length and colon weight-to-length ratio were used to determine the severity of colitis. Animals with colitis exhibited shorter colon lengths and a lower colon weight-to-length ratio than normal mice [
17]. LP-HFY11 might potentially reduce the changes in colon length and weight induced by colitis.
MPO is an enzyme widely present in white blood cells, mainly in the granular body of neutrophils. In colitis, inflammatory responses lead to the aggregation and activation of neutrophils, resulting in the release of a large amount of MPO. MPO plays an essential role in colitis and is closely related to the development of inflammation and tissue damage [
18]. It produces reactive oxygen species through oxidative reactions, such as hypochlorite ions and free radicals, which have a strong oxidative capacity and can cause the lipid peroxidation of cell membranes, leading to cell damage and further aggravating the inflammatory process [
19]. In addition, MPO also produces nitric oxide (NO) from nitrous oxide (NO) and is involved in the regulation of inflammatory signaling pathways [
20]. In colitis, excessive MPO production can damage the intestinal mucosal barrier, leading to cell damage and the further development of inflammation. Studies have shown that the level of MPO in the tissues of patients with colitis is closely related to the severity of inflammation, and high levels of MPO activity are associated with the activity and deterioration of the disease [
21]. GSH is an important antioxidant. In colitis, inflammatory reactions and oxidative stress can lead to a decrease in the GSH level. Many free radicals and oxidizing substances are produced in the inflammatory process of colitis, increasing the consumption of GSH within the cell and thereby reducing its antioxidant capacity [
22]. MDA is a product of lipid peroxidation and can cause lipid peroxidation in the cell membrane. In colitis, the production of MDA increases due to the increase in the inflammatory reaction and oxidative stress, aggravating the oxidative damage of the cell membrane and thus resulting in an impaired cell function. MDA, as a product of oxidative stress, can cause a further aggravation of inflammatory reactions [
23]. It can activate inflammatory cells, such as neutrophils and macrophages, and release inflammatory mediators and cytokines, thus causing the expansion and continuity of inflammatory reactions. In addition, MDA is also associated with tissue damage caused by inflammation, leading to damage to epithelial cells and the destruction of the mucosal barrier function [
24]. The regulatory effect of LP-HFY11 on the levels of MPO, NO, GSH, and MDA in mouse colon tissue may also be an essential mechanism underlying its alleviating effect on mouse colitis.
Colitis is intestinal tissue inflammation, and IL-2 is a cytokine promoting the inflammatory response. In colitis, immune cells produce a considerable amount of IL-2 in response to inflammation, exacerbating the inflammatory response. IL-2 is a key T-cell proliferation factor that promotes the proliferation and differentiation of CD
4+ helper T cells and regulates the activity of various T-cell subsets. Colitis is characterized by an imbalance and aberrant function of T cells, as well as a compromised mucosal barrier function, allowing bacteria and toxins to infiltrate and induce an inflammatory response [
25]. IL-2 regulates the immunological response of T cells and is vital for maintaining the immune balance and controlling intestinal inflammation. It is directly associated with the integrity of the intestinal mucosal barrier, emphasizing its importance in preventing the conditions that lead to colitis. IL-2 helps regulate the integrity of the mucosal barrier and maintain a proper intestinal function [
26]. In particular, IL-10 is essential for regulating intestinal inflammation and other immune responses. As macrophages are the primary target cells for the anti-inflammatory activity of IL-10, this impact is most noticeable in these cells. Second, IL-10 regulates the metabolic activities of macrophages to alleviate inflammation somewhat. It causes macrophages to switch from glycolysis to oxidative phosphorylation metabolism, which is linked to an anti-inflammatory phenotype. Third, mTOR inhibition is significantly aided by IL-10 [
27]. The maintenance of macrophage mitochondrial health and the promotion of phagocytosis depend on this suppression of mTOR. Finally, impaired IL-10 signaling causes the accumulation of damaged mitochondria in macrophages, which adds to the dysregulated inflammatory response seen in patients with inflammatory bowel disease [
28]. Hence, it is presumed that LP-HFY11 can regulate the validation cytokines in serum, thereby intervening in the development of colitis.
nNOS mainly exists in nerve tissue, and its function is to synthesize nitric oxide (NO). It regulates neural signal transmission by releasing NO. In colitis, nNOS is involved in regulating intestinal motility, blood flow, and the protection of intestinal mucosa [
29]. eNOS is mainly distributed in endothelial cells. It is responsible for synthesizing nitric oxide and plays a role in regulating vasodilation, as well as anti-inflammatory and anticoagulant effects. In colitis, eNOS is involved in regulating the intestinal blood flow, protecting the mucosal barrier, and inhibiting the inflammatory response [
30]. iNOS is mainly induced and expressed during the inflammatory process, and its synthesis ability is high, producing a large amount of NO. In colitis, the expression of iNOS is usually associated with an inflammatory response. It can participate in the bactericidal effect of inflammatory cells, regulate the immune response, and regulate inflammatory signaling pathways by releasing NO [
31]. nNOS, eNOS, and iNOS play important roles in colitis. They participate in regulating physiological and pathological processes, such as intestinal motility, blood flow, the mucosal barrier, and the inflammatory response, through NO synthesis [
32].
c-Kit is mainly expressed in intestinal interstitial cells (Cajal cells) and mucosal epithelial cells. It participates in regulating intestinal motility, maintaining mucosal barrier integrity, and regulating immune responses by binding to its ligand SCF [
33]. SCF is mainly produced by intestinal epithelial and stromal cells. It can bind to c-Kit receptors, promote the proliferation and differentiation of Cajal cells, regulate intestinal smooth muscle contraction and movement, and participate in intestinal repair and mucosal barrier protection [
34]. In colitis, the functions of c-Kit and SCF may be disrupted. The inflammatory response leads to the abnormal activation of the c-Kit signaling pathway and the abnormal expression of SCF. This may affect the normal motility of the intestine, the integrity of the mucosal barrier, and the regulation of the immune response, further exacerbating the inflammatory process [
35].
IL-8 is a chemotactic factor mainly produced by various cells, such as inflammatory, epithelial, and endothelial cells. Its primary purpose is to attract and activate white blood cells, particularly neutrophils, thus promoting their migration to the site of inflammation. Excessive IL-8 production can cause inflammation to persist, thus aggravating colitis [
36]. CXCR2 is an IL-8 receptor mainly expressed on the surface of white blood cells. When IL-8 binds to CXCR2, it activates the CXCR2 signaling pathway, triggering various inflammatory responses in cells [
37]. In colitis, the activation of CXCR2 can enhance neutrophil chemotaxis and activation, exacerbating the inflammatory response and causing tissue damage. The aberrant expression of IL-8 and CXCR2 may result in the increased aggregation and activation of inflammatory cells, prolonging and exacerbating the inflammatory response. As a result, blocking the IL-8 and CXCR2 signaling pathways may be a useful approach for treating colitis because it can reduce inflammation and tissue damage [
38]. The mRNA regulatory effect of LP-HFY11 on colon tissue can effectively intervene in the development of colitis in mice, thereby promoting functional recovery.
Dysfunction of gut microbiota is an essential factor leading to inflammation of the colon. A vast majority of bacteria in the human gut are composed of
Firmicutes and
Bacteroidetes, and a higher proportion of
Firmicutes than
Bacteroidetes can cause an increase in the levels of inflammatory factors in the blood, increasing the possibility of intestinal tissue damage [
39]. The gut
Firmicutes/
Bacteroidetes ratio (F/B) is widely believed to have an important impact on maintaining normal intestinal stability. Experimental colitis has shown that the F/B ratio in the gut increases after the induction of colitis, which can be used as an indicator to evaluate the stability of gut microbiota [
40].
Lactobacillus and
Bifidobacteria exert various bioactive effects, especially in protecting the normal metabolic state of the body, avoiding tissue damage caused by inflammation and other abnormalities and thus protecting the intestine [
41]. In addition, a healthy gut microbiota can improve the body’s resistance and tissue-repair ability by regulating various mechanisms, such as the immune function, and intervene in colitis [
42]. This study also confirmed that LP-HFY11 promoted the production of
Bacteroidetes and
Bifidobacteria in the mouse intestine, while supplementing with
Lactobacillus and reducing the expression of
Firmicutes and the F/B expression ratio, thereby inhibiting inflammation by regulating the intestinal microbiota and exerting an inhibitory effect on colitis formation. In particular, the side effects of gatifloxacin as a drug include symptoms such as nausea, diarrhea, abdominal pain, constipation, and indigestion. As a lactic acid bacteria isolated from food, LP-HFY11 has no side effects and has better application prospects.