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Using gut microbiota and non-targeted metabolomics techniques to study the effect of xylitol on alleviating DSS-induced inflammatory bowel disease in mice

BMC Immunology volume 26, Article number: 18 (2025) Cite this article

Abstract

Background

Inflammatory bowel disease (IBD) has become a global healthcare issue, with its incidence continuing to rise, but currently there is no complete cure. Xylitol is a widely used sweetener in various foods and beverages, but there is limited research on the effects of xylitol on IBD symptoms.

Aim

Study on the effect of oral xylitol in improving intestinal inflammation and damage in IBD mice, further explore the mechanism of xylitol in alleviating IBD symptoms using intestinal microbiota and non-targeted metabolomics techniques.

Methods

An IBD mouse model was induced using sodium dextran sulfate (DSS). After 30 days of oral administration of xylitol, we assessed the disease activity index (DAI) scores of mice in each group. The expression levels of inflammatory factors in the colon tissues were measured using qPCR. Additionally, we examined the damage to the intestinal mucosa and tight junction structures through HE staining and immunohistochemical staining. Finally, the alterations in the gut microbiota of the mice were analyzed using 16S rDNA sequencing technology.The production of three main short-chain fatty acids (SCFAs, including acetate, propionic acid and butyric acid) in feces and the changes of serum metabolomics were measured by non-targeted metabolomics techniques.

Results

The findings indicated that xylitol effectively mitigated weight loss and improved the DAI score in mice with IBD. Moreover, xylitol reduced the expressions of Caspase-1, IL-1β, and TNF-α in the colon tissue of the mice, and increased the expressions of ZO-1 and occludin in intestinal mucosal. Xylitol could enhance the variety of intestinal bacteria in IBD mice and influenced the abundance of different bacterial species. Additionally, metabolomic analysis revealed that oral xylitol increased the levels of three main SCFAs in the feces of IBD mice, while also impacting serum metabolites.

Conclusions

Our findings suggest that xylitol can help improve IBD symptoms. Xylitol can improve the intestinal flora of IBD mice and increase the production of SCFAs to play an anti-inflammatory role and protect the mucosal tight junction barrier. These discoveries present a fresh prophylactic treatment of IBD.

Clinical trial number

Not applicable.

Peer Review reports

Background

IBD is a long-term inflammatory disorder that mainly affects the digestive system, encompassing Crohn’s disease (CD) and ulcerative colitis (UC) [1, 2]. As non-developed countries and regions such as Asia, South America, and the Middle East have experienced industrialization and urbanization in the past few decades, IBD has become a worldwide ailment [3,4,5]. In China, there has been a notable rise in the occurrence of IBD in recent years, making it a common and frequently encountered illness [6].

The exact cause of IBD is still not fully understood and is believed to be influenced by genetic susceptibility, mucosal immunity, and the intestinal microecological environment [7, 8]. In recent years, there has been growing interest in exploring the connection between the intestinal microflora and the development of IBD [9, 10]. According to the prevailing theory, IBD is a result of an exaggerated immune response in individuals who are genetically predisposed, triggered by the presence of intestinal flora disorder. As a result, various microecological treatments have been investigated for their potential in managing IBD [11, 12].

Xylitol, a natural sugar alcohol, is commonly found in fruits and vegetables and can also be produced by the human body itself [13, 14]. It is widely recognized as a safe edible sweetener. Recent research has confirmed its health benefits, including lowering blood sugar levels and preventing dental caries [15, 16]. Xylitol has been widely used as the most important sucrose substitute in food production, including chewing gum, various beverages, and pastries. The total amount of xylitol consumed by IBD patients in their daily diet is increasing [17, 18]. A current unavoidable issue is whether xylitol has a beneficial or harmful impact on IBD patients.

With its low calorie content, only a small amount of xylitol is directly absorbed by the body, with 5% excreted [19, 20]. The majority of xylitol is digested by intestinal microorganisms, and its role in the intestinal tract should not be underestimated, though there is limited research in this area. In addition, based on the close relationship between intestinal dysbiosis and the onset and progression of IBD, exploring the role of xylitol in regulating the dysbiosis of intestinal flora in IBD patients is of great significance for the treatment and daily diet of IBD. This study induced IBD in mice through oral administration of dextran sulfate sodium (DSS), and elucidated the prophylactic treatment of xylitol on IBD in mice by analyzing its regulatory effect on intestinal flora and serum metabolomics disorders. The results of this study can provide guidance for the clinical treatment and daily diet of IBD, and provide theoretical support for the widespread use of xylitol as a sugar substitute.

Results

Xylitol improved body weight loss and DAI score deterioration in mice

When treated with DSS for 3 days, the IBD group mice showed significant soft stools. On the fifth day, mice in the IBD group tested positive for fecal occult blood. From day 7 onwards, the weight of mice in the IBD group was the lowest among the three groups. The mice in the xylitol group began to show obvious stool soft and fecal occult blood positive on the 5th day of the experiment. From day 5 of DSS induction, DAI scores were significantly higher in the IBD and xylitol groups than in the NC group, but no difference between the IBD and xylitol groups (Fig. 1).

Fig. 1
figure 1

Changes in mouse body weight and DAI score during the experiment. A: body weight changes; B: DAI score changes. a: compared with the NC group, P<0.05

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Xylitol reduces intestinal mucosal damage and increases the expressions of tight junction proteins ZO-1 and occludin

The HE staining and immunohistochemical staining results for ZO-1 and Occludin showed no differences between the NC group and the xylitol control group, indicating that adding 5% xylitol to the drinking water had no significant effect on the integrity of the intestinal mucosal barrier in mice (Fig 2).

Compared to the NC group, DSS mice had significantly shortened colonic villi, ulcers in the mucosa and submucosa, and infiltration of neutrophils and lymphocytes. The Xylitol group mice had normal colonic villi with only mild infiltration of neutrophils and lymphocytes, while the NC group mice showed no signs of inflammation (Fig. 4A-D).

ZO-1 and Occludin proteins are mainly expressed on the surface of intestinal mucosa, within the intestinal gland lumen, and between intestinal glands (Fig. 4E-L). Compared to the NC group, the DSS and Xylitol groups of mice showed significantly decreased expression of ZO-1 and Occludin on the surface of intestinal mucosa. Compared to the DSS group, the Xylitol group mice showed a significant increase in the expression of ZO-1 and Occludin on the surface of intestinal mucosa (P < 0.05) (Fig. 4M, N).

Fig. 2
figure 2

The results of mouse intestinal mucosa HE staining and tight junction proteins ZO-1 and Occludin immunohistochemical staining (n = 3). A: NC group HE staining; B: Xylitol Control group HE staining results; C: DSS group HE staining results; D: Xylitol group HE staining results; E: NC group ZO-1 immunohistochemical staining; F: Xylitol Control ZO-1 immunohistochemical staining; G: DSS group ZO-1 immunohistochemical staining; H: Xylitol group ZO-1 immunohistochemical staining; I: NC group Occludin immunohistochemical staining; J: Xylitol Control group Occludin immunohistochemical staining; K: DSS group Occludin immunohistochemical staining; L: Xylitol group Occludin immunohistochemical staining; M: ZO-1 protein expression level; N: Occludin protein expression level

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Xylitol suppressed pro-inflammatory cytokine expression in the colonic tissues of mice

Compared with the NC group, the expressions of NLRP3, Caspase-1, IL-1β and TNF-α were significantly increased in the DSS and xylitol groups (P < 0.05). Compared with the DSS group, the expressions of Caspase-1, IL-1β and TNF-α were significantly increased in the xylitol group (P < 0.05), and there was no significant change in NLRP3 expression (P>0.05) (Fig. 3).

Fig. 3
figure 3

The mRNA expressions of proinflammatory cytokines in mouse colon tissue (n = 6). A: NLRP3; B: Caspase-1; C: IL-1β; D: TNF-α. a: compared with the NC group, P<0.05; b: compared with the DSS group, P<0.05

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Xylitol increased the productions of three main SCFAs in the mouse colon

Compared with the NC group, the concentrations of acetic acid and butyric acid in the colon contents of the DSS group significantly decreased (P < 0.05), and no significant change in propionate concentration (P > 0.05). The concentrations of acetic acid and butyrate in the colon contents of the xylitol group were significantly higher than those of the NC and DSS groups (P < 0.05), and the concentration of propionic acid was only significantly higher than that of the DSS group (P < 0.05) (Fig. 4).

Fig. 4
figure 4

Concentrations of acetic acid, propionic acid, and butyric acid in the mouse colonic contents (n = 6). A: acetic concentration; B: propionic acid concentration; C: butyric acid concentration. a: compared with the NC group, P<0.05; b: compared with the DSS group, P<0.05

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Effects of xylitol on the intestinal microbiota of IBD mice

Gut microbes participate in various host physiological activities including immune defense, nutrition, metabolism and immune regulation. In this study, we explored the effect of xylitol on the intestinal flora of IBD mice. As shown in Fig. 5A-D, there was significant difference in intestinal flora α diversity between the NC and xylitol groups (P<0.05), but no significant difference between other groups (P>0.05). In terms of β diversity, the PCA scatter plot and PCoA scatter plot showed that the NC group was significantly separated from the DSS and xylitol groups, and the xylitol group was between the NC and DSS groups, indicating that the intestinal flora of the NC group was significantly different from the DSS and xylitol groups, and xylitol could improve the intestinal flora diversity of IBD mice (Fig. 5E and F).

The mouse intestinal flora was further analyzed at the phylum and genus levels (Fig. 5G and H). At the phylum level, Fimicutes abundance was significantly lower in the DSS and xylitol groups compared with the NC group (P < 0.05). At the genus level, the Akkesmansia and Allobaculum abundance was significantly higher in the DSS and xylitol group compared with the NC group. Compared with the NC group, the abundances of Bilophila, Odoribacter, Oscillospira and Prevotrllaceae were significantly decreased in DSS group (P < 0.05). Compared with the DSS group, Allobaculum, Streptococcus abundance were significantly reduced in the Xylitol group, while Odoribacter abundance were significantly increased (P < 0.05). There was no significant change in the abundance of Gemmatimonadetes in the colon contents of the 3 groups (Fig. 6).

Fig. 5
figure 5

Results of intestinal flora detection in mice (n = 6). A: α diversity (Shannon index). B: α diversity (Simpson index). C: α diversity (Chao1 index). D: α diversity (ACE index). E: PCA scatter plot. F: PCoA scatter plot. G: phylum level clustering heat map; H: genus level clustering heat map. a: compared with the NC group, P<0.05

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Fig. 6
figure 6

Changes in the abundance of important bacteria in the intestinal flora of mice at phylum and genus levels (n = 6). A: Fimicutes; B: Gemmatimonadetes; C: Akkesmansia; D: Allobaculum; E: Bilophila; F: Odoribacter; G: Oscillospira; H: Prevotrllaceae; I: Parabacteroides; J: Streptococcus. a: compared with the NC group, P<0.05; b: compared with the DSS group, P<0.05

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Effects of xylitol on serum metabolomics in IBD mice

The various metabolites in mouse serum were analyzed by UPLC-Q-TOF-MS to explore the effect of xylitol on serum metabolites in IBD mice. The PCA plot indicated a better separation between samples from the the NC, DSS, and xylitol groups. Further using OPLS-DA analysis revealed significant separation between the NC and DSS groups, the NC and xylitol groups, the DSS and xylitol groups. The differential metabolites were screened using the rule of VIP > 1 and P < 0.05 (Fig. 7).

From the PCA scatter plot, the samples of the NC and DSS groups could not be completely distinguished, and the samples of the DSS and xylitol groups could be significantly distinguished without outlier samples. For further OPLS-DA analysis, the abscissa was the predicted principal component score and the ordinate was the orthogonal principal component score. As shown in the Fig. 7, the DSS group coud be separated from the xylitol group (ESI− R2X = 0.507, R2Y = 0.316, Q2 = 0.76). The above results showed that the metabolites between the NC and DSS groups, and the DSS and xylitol groups were significantly different.

23 differential metabolites were screened from the NC and DSS groups (Table 1). Compared with the NC group, the main metabolites up-regulated in the DSS group were 5b-Cholestane-3a, 7a, 12a, 23 S, 25-pentol, 3a, 7b, 21-Trihydroxy-5b-cholanoic acid, Myristoylglycine and 19-Norandrosterone; the main metabolites down-regulated were Enkephalin L and Mevalonic acid.

24 different metabolites were screened from serum of the DSS group and xylitol groups (Table 2). Compared with the DSS group, Oleoyl glycine, Nervonic acid, Oleic acid and Pantothenic acid were the main metabolites up-regulated in serum of the xylitol group, while Palmitoyl glucuronide and Norepinephrine sulfate were also down-regulated. The clustering heat map could reflect the increase or decrease of the relative content of different metabolites in each group. Compared with the NC group, the relative content of differential metabolites in the DSS group was significantly changed, and the intervention of xylitol could reverse this change.

The metabolic pathways of the differential metabolites between the NC and DSS groups, the DSS and xylitol group were analyzed, and a total of 6 related metabolic pathways were found, namely D-glutamine and D-glutamate metabolism, nitrogen metabolism, purine metabolism, tryptophan metabolism, primary bile acid biosynthesis and biotin metabolism. Xylitol can reverse the metabolic pathways that are disrupted by DSS (Fig. 8).

Table 1 Differential metabolites between the NC and DSS groups
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Table 2 Differential metabolites between the DSS and xylitol groups
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Fig. 7
figure 7

Mouse serum metabolites PCA plot and OPLS-DA plot. A: PCA plot; B: OPLS-DA plot of the NC and DSS groups; C: OPLS-DA plot of the NC and xylitol groups; D: OPLS-DA plot of the DSS and xylitol groups

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Fig. 8
figure 8

Differential metabolites and related metabolic pathways in mouse serum. A: Map of differential metabolite percentage accumulation in mouse serum; B: Clustering heat map of differential metabolites in mouse serum; C: Analysis of metabolic pathways of differential metabolites in the NC and DSS groups mouse serum. 1: Tryptophan metabolism. 2: Primary bile acid biosynthesis. 3: D-glutamine and D-glutamate metabolism. 4: Ammonia metabolism. 5: Purine metabolism. 6: Sphingolipid metabolism. D: Analysis of metabolic pathways of differential metabolites in the DSS and xylitol groups mouse serum. 1: D-glutamine and D-glutamate metabolism. 2: Ammonia metabolism. 3: Pyrimidine metabolism. 4: Tryptophan metabolism. 5: Primary bile acid biosynthesis. 6: Purine metabolism. 7: Glycolysis/gluconeogenesis

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Disscussion

With the increasing use of sugar substitutes in food and beverages, there is a growing concern for the safety of these alternatives [21, 22]. Xylitol, derived from agricultural crops like corncob and bagasse, is a commonly used sugar substitute. It is a natural sweetener and has been internationally recognized as a safe food substance [23, 24]. Unlike other sugar substitutes, xylitol not only provides sweetness but also has nutritional value. It is the sweetest among all polyols and its sweetness is comparable to sucrose. Additionally, xylitol is an intermediate of human sugar metabolism [25, 26]. Even in a healthy individual who does not consume xylitol-containing foods, there is still a small amount of xylitol present in their blood (0.03 to 0.06 mg per 100 mL), and the human liver can produce 5 g to 15 g of xylitol per day [27]. Since xylitol is a normal part of sugar metabolism in the body and does not require insulin for its metabolic process, it can be safely consumed by diabetic patients without causing a rise in blood sugar levels.

The existing research on xylitol suggests that it has numerous benefits in the food and pharmaceutical industries as a sugar substitute, as well as in preventing dental and physical diseases [28]. Xylitol has been found to have a significant anti-plaque effect on teeth and can help reduce gum inflammation [27]. It also acts as a preventive agent for dental caries by inhibiting the growth of harmful bacteria [29]. Moreover, xylitol has shown potential in reducing constipation, diabetes, obesity, and other physical ailments, indicating its positive impact on the digestive and immune systems in humans [30, 31]. However, there is currently no research on the effects of xylitol on inflammatory bowel disease.

Additionally, further investigation revealed that xylitol significantly inhibited the expression of Caspase-1, IL-1β, and TNF-α in the colon tissue of IBD mice, indicating its ability to reduce inflammatory damage to the colon mucosa. Furthermore, LC-MS/MS analysis of mouse feces showed that oral xylitol increased the production of acetic acid, propionic acid, and butyric acid. This finding aligns with previous research reporting the prebiotic function of xylitol [27, 29, 31]. Short-chain fatty acids (SCFAs), including acetic acid, propionic acid, and butyric acid, are organic acids produced by anaerobic bacteria during the fermentation of dietary fiber and resistant starch in the colon [32]. The characteristic of IBD is the alteration in the composition of the intestinal microbiota, with a significant decrease in the number of bacteria producing SCFAs, including bacteria from the Firmicutes phylum such as Lachnospiraceae and Ruminococcaceae [33, 34]. Numerous studies have highlighted the diverse biological functions of SCFAs, including anti-infection, anti-tumor, and anti-inflammatory properties, with particular emphasis on their anti-inflammatory effects [35, 36]. Based on these findings, we propose that xylitol may undergo anaerobic fermentation in the colon, leading to the production of SCFAs.

The anaerobic bacteria Bacteroides in the colon primarily produce acetic acid and propionic acid [37, 38], while Firmicutes mainly produce butyric acid [39]. These SCFAs have the ability to regulate intestinal mucosal immunity by influencing the function of various immune cells [40, 41]. In cases of acute inflammation, the balance of intestinal immune homeostasis is disrupted, leading to the release of pro-inflammatory cytokines such as IL-6, IL-8, and IL-17. These cytokines further contribute to intestinal inflammation. However, SCFAs can counteract this inflammatory response by inhibiting the production of pro-inflammatory cytokines like TNF-α, IL-6, and IL-12. This inhibition is achieved through the HDACs pathway or activation of the GPCR41/43 pathway [42]. Additionally, SCFAs can down-regulate the expression of inducible nitric oxide synthase (iNOS), vascular cell adhesion molecule-1 (VCAM-1), intracellular adhesion molecules (ICAM-1), and other chemokines. This down-regulation promotes the secretion of anti-inflammatory factors such as IL-10 and IL-4 by intestinal immune cells [43]. Going forward, our study will further explore the production of these three SCFAs in the colon of mice with varying levels of xylitol intake.

The results of 16S rDNA sequencing of mouse colon contents in this study also support that oral xylitol can increase SCFAs production in colon and inhibit intestinal inflammation. The abundance of TM7 and Fimicutes in the colon of mice increased after oral administration of xylitol. Both TM7 and Fimicutes are associated with the production of SCFAs in the gut [44]. After oral administration of fructooligosaccharide, TM7 abundance and SCFAs production increased significantly [45]. When mice were fed a diet rich in resistant starch, the abundance of Fimucutes in the colon was also increased, as was the concentration of SCFAs [46]. Allobaculum is a specific marker bacteria in the stool of patients with inflammatory bowel disease, and its abundance was significantly increased in the stool of patients with IBD. In this study, we also found that the abundance of Allobaculum was significantly increased in the colon contents of mice induced by DSS [47, 48]. Streptococcus in the gut is a pathogenic bacterium that is generally considered to be one of the causes of IBD [49]. Previous studies have shown that the severity of ulcerative enteritis is proportional to the level of Streptococcus related antibodies in patients. It is worth noting that Streptococcus is also a colonizing bacterium in the human oral pharynx, and Streptococcus in the intestine is probably derived from ectopic colonization by oral pharyngeal bacteria [50]. Therefore, the role of oral Streptococcus and pharyngeal bacteria in the pathogenesis of IBD is a problem worthy of further study.

Further non-targeted metabolomics studies showed that xylitol can regulate D-glutamine and D-glutamic acid metabolism, primary bile acid biosynthesis metabolism, tryptophan metabolism, nitrogen metabolism, purine metabolism and biotin metabolism in IBD mice, which may improve the symptoms of IBD mice through the above metabolic pathways. Among the screened differential metabolites, the role of Oleoyl glycine in the inflammatory response was unclear, but its serum concentration was reduced in IBD patients [51, 52]. In this study, the serum Oleoyl glycine level in the xylitol group was significantly up-regulated compared with the DSS group, which may be related to the treatment of IBD by xylitol, but the exact mechanism remains to be further studied.

Nervonic acid is a lipid metabolite that is significantly reduced in vivo during acute and chronic inflammation [53], possibly due to the inhibition of lipid metabolism during inflammation and the conversion to the synthesis of the pro-inflammatory metabolite arachidonic acid, which results in a substrate deficiency leading to Nervonic acid synthesis [54]. We hypothesize that the high level of inflammation in IBD patients leads to the obstruction of lipid metabolism in the liver, forcing the synthesis of many beneficial fatty acids (such as Nervonic acid) to shift to the synthesis of pro-inflammatory lipids. There is a high level of inflammation in obese patients, where multiple pro-inflammatory lipid metabolites (such as Omega-6 fatty acids) accumulate and further aggravate the inflammatory response [55]. In addition, we also noted a significant increase in Oleic acid levels in IBD mice after oral xylitol. Studies have shown that appropriate concentrations of Oleic acid can significantly inhibit various chronic inflammatory reactions [56, 57], which may be related to xylitol improving IBD symptoms.

Palmitoyl glucuronide is a specific metabolite in the serum of patients with ulcerative colitis, and its concentration is proportional to the severity of ulcerative colitis and is related to the level of chronic inflammation in patients [58, 59]. In this study, we found that the Palmitoyl glucuronide level in IBD mice was significantly reduced after oral administration of xylitol, which may also be related to the ability of xylitol to inhibit chronic inflammatory response, but the exact mechanism remains to be further studied.

In this study, we noted an interesting phenomenon of significantly increased pantothenic acid levels in IBD mice that took xylitol orally. Studies have shown that the deficiency of dietary nutrients such as pantothenic acid and zinc can aggravate IBD symptoms, and the symptoms can improve after supplementation of nutrients such as pantothenic acid [60]. Other studies have found that nutrition-related amino acid metabolism, nitrogen metabolism, purine metabolism, etc. can affect the occurrence and development of IBD [61], which also provides a new idea for the study of the pathogenesis and treatment of IBD. Our xylitol study also provides a pathway for the prevention and prophylactic treatment of IBD.

Conclusion

Xylitol is a common dietary additive, and the intake of xylitol is increasing in modern society. IBD is a kind of chronic disease closely related to the living habits of modern society, and there is no cure. Our results show that oral xylitol does not aggravate IBD symptoms, but inhibits colon inflammation and protected the And protect the intestinal mucosa tight junction structure. Xylitol, similar to prebiotics, can increase the production of three main SCFAs in the colon and exert its anti-inflammatory ability. Intestinal flora sequencing analysis showed that xylitol could improve intestinal flora diversity and increase the abundance of SCFAs-producing bacteria in IBD mice. Metabolomics analysis showed that xylitol can regulate the disordered D-glutamine and D-glutamate metabolism, primary bile acid biosynthesis metabolism, tryptophan metabolism, nitrogen metabolism, purine metabolism and biotin metabolism in IBD mice, which may be related to the improvement of IBD symptoms, but the exact mechanism remains to be further studied. However, the conclusion that existing xylitol can improve IBD is still based on research results from animal models. The next stage requires conducting corresponding clinical studies to confirm the impact of xylitol on IBD.

Methods

Experimental animals and groups

The male ICR mice (22 g ± 4 g) were purchased from Nanjing Wukong Biotechnology Co., Ltd. (Nanjing, China) and were maintained in the Experimental Animal Center of Jiangsu University. Relevant studies were conducted after approval by the Ethics Committee and the Experimental Animal Management and Use Committee of Jiangsu University (protocol code UJSIACUC-AP-2022032016). IBD in mice was induced by oral dextran sodium sulfate (DSS, CAS: 9011-18-1, MP Biomdicals, California, USA), as follows. The xylitol was purchased from Sigma-Aldrich (>99%, CAS: 87-99-0, USA). ICR mice were randomly divided into 3 groups, including normal control group (NC group), DSS group and xylitol group, with 6 mice in each group. Mice in the NC group were given sterilized purified water, the IBD and xylitol groups mice were given the water with 3% DSS (v/v) and drinking for 1 week to induce IBD. Referring to the xylitol experimental concentration of other scholars, mice in the xylitol group were given the water with 5% xylitol (v/v) and drinking for one month before inducing IBD [25, 62]. To further verify that oral 5% xylitol has no effect on the intestinal mucosal function of mice, we established a xylitol control group. Mice in this group continuously drank distilled water containing 5% xylitol for 30 days, and the integrity of their intestinal mucosal barrier was assessed using HE staining and immunohistochemical staining. From the 5th week, the xylitol group mice were supplemented with 3% DSS to induce IBD. Mouse weight changes, fecal traits and occult blood in feces were recorded from when the DSS was added to drinking water. At the end of the experiment, the mice were euthanized by intraperitoneal injection of Urethan (Sigma-Aldrich, St. Louis, MO, USA, 700 mg/kg), the serum and colon contents of mice were collected, and part of the colon tissue was collected for RNA extraction and qPCR analysis.

Mouse intestinal tissue HE and immunohistochemical staining

Mouse colon tissue was fixed with 4% paraformaldehyde and dehydrated with alcohol, followed by embedding in paraffin. After dewaxing with xylene, the tissue was stained with hematoxylin and eosin (HE staining). After staining, the samples were sealed with neutral gum and observed under a microscope to observe the morphological changes in the mouse colon tissue. Immunohistochemistry was used to evaluate the expression levels of the tight junction proteins including ZO-1 and Occludin in mouse colon tissue. The antibodies of ZO-1 and Occludin were provided by Boster Biological Technology Co.,Ltd (Wuhan, China), and the antibodies were diluted 1:200 for use. After dewaxing the mouse colon tissue slices, the activity of peroxidase in the samples was quenched with 3% hydrogen peroxide. After antigen retrieval, the samples were blocked with goat serum for 30 min and then used for ZO-1 and Occludin protein immunohistochemical staining. Using Image-Pro Plus image analysis software to measure the average integrated optical density of positive products in the intestinal mucosa of each group of mice, the expression levels of ZO-1 and Occludin proteins are reflected by the size of the average integrated optical density value.

QPCR assay

The total RNA kit (RC101, Vazyme, Nanjing, China) was used to extract RNA from colon tissue. Then, 1 µg of the total RNA was transcribed into cDNA using the HiScript III 1st Strand cDNA Synthesis Kit (R323-01, Vazyme, Nanjing, China). The expression levels of the target genes were determined using the AceQ Universal SYBR qPCR Master Mix Kit (Q111-02, Vazyme, Nanjing, China). The primers were synthesized by Suzhou GENEWIZ Company, and their sequences are as follows (Table 3): The qPCR reaction system consisted of 10 µL SYBR Master Mix, 0.4 µL of upstream and downstream primers (10 µmol/L), and 1 µL of cDNA. The reaction was predenatured at 95 °C for 20 s, denatured at 95 °C for 5 s, annealed at 60 °C for 20 s, and extended at 72 °C for 30 s for 40 cycles. Each sample was repeated three times, and β − actin gene was used as the internal reference to calculate the relative expressions of each target proinflammatory cytokines gene in mouse colon tissue by formula 2−ΔΔCt.

Table 3 The qPCR primers sequences for mice
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IBD model severity score

The IBD severity, including weight loss, hematochezia and stool, was assessed by DAI scoring criteria as shown in Table 4. Mouse fecal occult blood was tested by the O-linked toluidine method kit (ML095013, Shanghai yuanye Bio-Technology Co., Ltd, Shanghai, China) according to the instructions of the kit. Fresh feces from mice were collected daily by adding 2 drops of reagent A (O-toluidine solution), then 2 drops of reagent B (hydrogen peroxide solution) to observe the results immediately. Dark blue in 10 s (+ +) is strong, blue green (+), no blue in 3 min is negative (-).

Table 4 DAI scoring criteria of mouse IBD model
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Analysis of the mouse intestinal microbiota

At the end of the experiment, mouse colon contents were collected and flash-frozen in liquid nitrogen and then transported to Wekemo Tech Group Co., Ltd. (Shenzhen, China) for detection and analysis. Using the fecal genomic DNA extraction kit (TIANGEN, Beijing, China), DNA was extracted from the contents of the mouse colon according to the steps outlined in the manual. The samples were then subjected to PCR amplification and sequencing analysis. The primers 341 F (CCTACGGGNGGCWGCAG) and 805R (GACTACHVGGGTATCTAATCC) were used to amplify the V3-V4 region of the 16S rRNA gene from the samples. High-quality sequences obtained after amplification were filtered through quality control to remove sequences that did not meet the criteria. The resulting samples were analyzed for OUT clustering, species classification, and differential microbial community analysis. Experimental data from were analyzed on the free online platform of Wekemo Bioincloud (https://www.bioincloud.tech/).

Metabolomics analysis of mouse serum

Blood was collected at room temperature for 30 min and centrifuged at 7 100×g for 10 min before separating the upper serum for metabolomics analysis. In metabolomics analysis, 200 µL of serum was mixed with 600 µL of methanol and centrifuged at 11 300 ×g for 15 min at 4 ℃, drawing 300 µL of supernatant from each sample for UPLC-Q/TOF-MS assay (Agilent 6538 Q-TOF-MS, USA), and see the supplement for details. Metabolomic analysis was performed by Wekemo Tech Group Co., Ltd. (Shenzhen, China). The data were analyzed on the free online platform of Wekemo Bioincloud (https://www.bioincloud.tech/).

The acetic acid, propionic acid, and butyric acid detection in mice serum were performed at Health Testing Center, Zhenjiang Center for Disease Control and Prevention (Zhenjiang, China) using liquid chromatography − mass spectrometry (LC − MS/MS) following He’s method [63], and see the supplement for details.

Statistical analysis and metabolomics data analysis

Data analysis was performed using the SPSS 20.0 statistical software. Measurement data are expressed as mean ± standard deviation. One-way ANOVA for comparison between multiple groups, and the least significant difference (LSD) method was used for the comparison between the two sample groups. In P < 0.05 was considered statistically significant.

For the metabolomics data analysis, the chromatograms of serum samples were extracted using Markerview 2.1 software and the peak area was normalized. The normalized data were subjected to principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA). The Differential metabolites were screened by the variable important in projection (VIP) values of the OPLS-DA model variables, and the endogenous differential metabolites were screened by VIP > 1 and P < 0.05 rules. Pathway analysis of the discovered differential metabolites was performed by MetaboAnalyst 3.0, further combined with the Kyoto Encyclopedia of Genes and Genomes (KEGG) database (https://www.kegg.jp/kegg/kegg1.html) and Human Metabolome Database (HMDB) database (https://hmdb.ca/) to resolve the biological significance of the differential metabolites, and finally identified potential biomarkers and related metabolic pathways closely related to IBD mouse induced by DSS and treated with xylitol.

Data availability

The datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request. The 16S rRNA sequence raw data of this study have been deposited in Genome Sequence Archive (PRJCA036199).

Abbreviations

IBD:

Inflammatory bowel disease

DAI:

Disease activity index

DSS:

Sodium dextran sulfate

SCFAs:

Short-chain fatty acids

CD:

Crohn’s disease

UC:

Ulcerative colitis

NLRP3:

Nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domain-containing protein 3

IL-1β:

Interleukin-1β

TNF-α:

Tumor necrosis factor-α

ZO-1:

Zona Occludens-1

PCA:

Principal component analysis

PCoA:

Principal coordinate analysis

OPLS-DA:

Orthogonal partial least squares-discriminant analysis

VIP:

Variable importance in the projection

References

  1. Al-Bawardy B, Shivashankar R, Proctor DD. Novel and emerging therapies for inflammatory bowel disease. Front Pharmacol. 2021;12:651415.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Levine A, Rhodes JM, Lindsay JO, Abreu MT, Kamm MA, Gibson PR, Gasche C, Silverberg MS, Mahadevan U, Boneh RS, et al. Dietary guidance from the international organization for the study of inflammatory bowel diseases. Clin Gastroenterol Hepatol. 2020;18(6):1381–92.

    Article  PubMed  Google Scholar 

  3. Mak WY, Zhao M, Ng SC, Burisch J. The epidemiology of inflammatory bowel disease: East Meets West. J Gastroenterol Hepatol. 2020;35(3):380–9.

    Article  PubMed  Google Scholar 

  4. Narula N, Wong E, Dehghan M, Mente A, Rangarajan S, Lanas F, Lopez-Jaramillo P, Rohatgi P, Lakshmi P, Varma RP, et al. Association of ultra-processed food intake with risk of inflammatory bowel disease: prospective cohort study. BMJ. 2021;374:n1554.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Bischoff SC, Escher J, Hébuterne X, Kłęk S, Krznaric Z, Schneider S, Shamir R, Stardelova K, Wierdsma N, Wiskin AE, et al. ESPEN practical guideline: clinical nutrition in inflammatory bowel disease. Clin Nutr. 2020;39(3):632–53.

    Article  PubMed  Google Scholar 

  6. Cai Z, Wang S, Li J. Treatment of inflammatory bowel disease: A comprehensive review. Front Med (Lausanne). 2021;8:765474.

    Article  PubMed  Google Scholar 

  7. Guan Q. A comprehensive review and update on the pathogenesis of inflammatory bowel disease. J Immunol Res 2019, 2019:7247238.

  8. Guo XY, Liu XJ, Hao JY. Gut microbiota in ulcerative colitis: insights on pathogenesis and treatment. J Dig Dis. 2020;21(3):147–59.

    Article  PubMed  Google Scholar 

  9. Wark G, Samocha-Bonet D, Ghaly S, Danta M. The role of diet in the pathogenesis and management of inflammatory bowel disease: A review. Nutrients. 2020;13(1):135.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Matsuoka K, Kanai T. The gut microbiota and inflammatory bowel disease. Semin Immunopathol. 2015;37(1):47–55.

    Article  CAS  PubMed  Google Scholar 

  11. Elson CO, Cong Y. Host-microbiota interactions in inflammatory bowel disease. Gut Microbes. 2012;3(4):332–44.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Amoroso C, Perillo F, Strati F, Fantini MC, Caprioli F, Facciotti F. The role of gut microbiota biomodulators on mucosal immunity and intestinal inflammation. Cells. 2020;9(5):1234.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Mushtaq Z, Imran M, Salim-ur-Rehman, Zahoor T, Ahmad RS, Arshad MU. Biochemical perspectives of xylitol extracted from Indigenous agricultural by-product mung bean (Vigna radiata) hulls in a rat model. J Sci Food Agric. 2014;94(5):969–74.

    Article  CAS  PubMed  Google Scholar 

  14. Im JH, Lee MK, Lee HI. Physicochemical and sensory properties and antioxidant activity of xylitol candies containing Yuja (Citrus junos) peels or pulp. Foods. 2024;13(15):2396.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. McCORMICK DB, TOUSTER O. The conversion in vivo of xylitol to glycogen via the Pentose phosphate pathway. J Biol Chem. 1957;229(1):451–61.

    Article  CAS  PubMed  Google Scholar 

  16. Asakura T, Adachi K, Minagami S, Yoshikawa H. Non-glycolytic sugar metabolism in human erythrocytes. I. Xylitol metabolism. J Biochem. 1967;62(2):184–93.

    Article  CAS  PubMed  Google Scholar 

  17. Simões CD, Maganinho M, Sousa AS. FODMAPs, inflammatory bowel disease and gut microbiota: updated overview on the current evidence. Eur J Nutr. 2022;61(3):1187–98.

    Article  PubMed  Google Scholar 

  18. Ruiz-Ojeda FJ, Plaza-Díaz J, Sáez-Lara MJ, Gil A. Effects of sweeteners on the gut microbiota: A review of experimental studies and clinical trials. Adv Nutr. 2019;10(suppl1):S31–48.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Wölnerhanssen BK, Meyer-Gerspach AC, Beglinger C, Islam MS. Metabolic effects of the natural sweeteners xylitol and erythritol: A comprehensive review. Crit Rev Food Sci Nutr. 2020;60(12):1986–98.

    Article  PubMed  Google Scholar 

  20. Zuo QL, Cai X, Zheng XY, Chen DS, Li M, Liu ZQ, Chen KQ, Han FF, Zhu X. Influences of xylitol consumption at different dosages on intestinal tissues and gut microbiota in rats. J Agric Food Chem. 2021;69(40):12002–11.

    Article  CAS  PubMed  Google Scholar 

  21. Msomi NZ, Erukainure OL, Islam MS. Suitability of sugar alcohols as antidiabetic supplements: A review. J Food Drug Anal. 2021;29(1):1–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Saraiva A, Carrascosa C, Raheem D, Ramos F, Raposo A. Natural sweeteners: the relevance of food naturalness for consumers, food security aspects, sustainability and health impacts. Int J Environ Res Public Health. 2020;17(17):6285.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Bordier V, Teysseire F, Schlotterbeck G, Senner F, Beglinger C, Meyer-Gerspach AC, Wölnerhanssen BK. Effect of a chronic intake of the natural sweeteners xylitol and erythritol on glucose absorption in humans with obesity. Nutrients. 2021;13(11):3950.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Bordier V, Teysseire F, Senner F, Schlotterbeck G, Drewe J, Beglinger C, Wölnerhanssen BK, Meyer-Gerspach AC. Absorption and metabolism of the natural sweeteners erythritol and xylitol in humans: A dose-ranging study. Int J Mol Sci. 2022;23(17):9867.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Xiang S, Ye K, Li M, Ying J, Wang H, Han J, Shi L, Xiao J, Shen Y, Feng X, et al. Xylitol enhances synthesis of propionate in the colon via cross-feeding of gut microbiota. Microbiome. 2021;9(1):62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Rawi MH, Zaman SA, Pa’ee KF, Leong SS, Sarbini SR. Prebiotics metabolism by gut-isolated probiotics. J Food Sci Technol. 2020;57(8):2786–99.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Salli K, Lehtinen MJ, Tiihonen K, Ouwehand AC. Xylitol’s health benefits beyond dental health: A comprehensive review. Nutrients. 2019;11(8):1813.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Gasmi Benahmed A, Gasmi A, Arshad M, Shanaida M, Lysiuk R, Peana M, Pshyk-Titko I, Adamiv S, Shanaida Y, Bjørklund G. Health benefits of xylitol. Appl Microbiol Biotechnol. 2020;104(17):7225–37.

    Article  CAS  PubMed  Google Scholar 

  29. Janket SJ, Benwait J, Isaac P, Ackerson LK, Meurman JH. Oral and systemic effects of xylitol consumption. Caries Res. 2019;53(5):491–501.

    Article  CAS  PubMed  Google Scholar 

  30. Rahman MA, Islam MS. Xylitol improves pancreatic Islets morphology to ameliorate type 2 diabetes in rats: a dose response study. J Food Sci. 2014;79(7):H1436–1442.

    Article  CAS  PubMed  Google Scholar 

  31. Yi EY, Kim YJ. Xylitol inhibits in vitro and in vivo angiogenesis by suppressing the NF-κB and Akt signaling pathways. Int J Oncol. 2013;43(1):315–20.

    Article  CAS  PubMed  Google Scholar 

  32. Markowiak-Kopeć P, Śliżewska K. The effect of probiotics on the production of short-chain fatty acids by human intestinal Microbiome. Nutrients. 2020;12(4):1107.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Zhou J, Li M, Chen Q, Li X, Chen L, Dong Z, Zhu W, Yang Y, Liu Z, Chen Q. Programmable probiotics modulate inflammation and gut microbiota for inflammatory bowel disease treatment after effective oral delivery. Nat Commun. 2022;13(1):3432.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Ekstedt N, Jamioł-Milc D, Pieczyńska J. Importance of gut microbiota in patients with inflammatory bowel disease. Nutrients. 2024;16(13):2092.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Yao Y, Cai X, Fei W, Ye Y, Zhao M, Zheng C. The role of short-chain fatty acids in immunity, inflammation and metabolism. Crit Rev Food Sci Nutr. 2022;62(1):1–12.

    Article  CAS  PubMed  Google Scholar 

  36. He J, Zhang P, Shen L, Niu L, Tan Y, Chen L, Zhao Y, Bai L, Hao X, Li X et al. Short-chain fatty acids and their association with signalling pathways in inflammation, glucose and lipid metabolism. Int J Mol Sci. 2020; 21(17).

  37. Chen SJ, Chen CC, Liao HY, Lin YT, Wu YW, Liou JM, Wu MS, Kuo CH, Lin CH. Association of fecal and plasma levels of short-chain fatty acids with gut microbiota and clinical severity in patients with Parkinson disease. Neurology. 2022;98(8):e848–58.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Xu M, Lan R, Qiao L, Lin X, Hu D, Zhang S, Yang J, Zhou J, Ren Z, Li X, et al. Bacteroides vulgatus ameliorates lipid metabolic disorders and modulates gut microbial composition in hyperlipidemic rats. Microbiol Spectr. 2023;11(1):e0251722.

    Article  PubMed  Google Scholar 

  39. Sun Y, Zhang S, Nie Q, He H, Tan H, Geng F, Ji H, Hu J, Nie S. Gut firmicutes: relationship with dietary fiber and role in host homeostasis. Crit Rev Food Sci Nutr. 2022;12:1–16.

    CAS  Google Scholar 

  40. Wenzel TJ, Gates EJ, Ranger AL, Klegeris A. Short-chain fatty acids (SCFAs) alone or in combination regulate select immune functions of microglia-like cells. Mol Cell Neurosci. 2020;105:103493.

    Article  CAS  PubMed  Google Scholar 

  41. van der Hee B, Wells JM. Microbial regulation of host physiology by short-chain fatty acids. Trends Microbiol. 2021;29(8):700–12.

    Article  PubMed  Google Scholar 

  42. Huang W, Man Y, Gao C, Zhou L, Gu J, Xu H, Wan Q, Long Y, Chai L, Xu Y et al. Short-chain fatty acids Ameliorate diabetic nephropathy via GPR43-mediated inhibition of oxidative stress and NF-κB signaling. Oxid Med Cell Longev 2020, 2020:4074832.

  43. Li B, Zhang B, Li Z, Li S, Li J, Wang A, Hou J, Xu J, Zhang R. Ginkgolide C attenuates cerebral ischemia/reperfusion-induced inflammatory impairments by suppressing CD40/NF-κB pathway. J Ethnopharmacol. 2023;312:116537.

    Article  CAS  PubMed  Google Scholar 

  44. Houtman TA, Eckermann HA, Smidt H, de Weerth C. Gut microbiota and BMI throughout childhood: the role of firmicutes, bacteroidetes, and short-chain fatty acid producers. Sci Rep. 2022;12(1):3140.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Wang L, Hu L, Yan S, Jiang T, Fang S, Wang G, Zhao J, Zhang H, Chen W. Effects of different oligosaccharides at various dosages on the composition of gut microbiota and short-chain fatty acids in mice with constipation. Food Funct. 2017;8(5):1966–78.

    Article  CAS  PubMed  Google Scholar 

  46. Zhu K, Fan H, Zeng S, Nie S, Zhang Y, Tan L, Li C, Xu F, Liu Q, Wu G. Polysaccharide from Artocarpus heterophyllus lam. (jackfruit) pulp modulates gut microbiota composition and improves short-chain fatty acids production. Food Chem. 2021;364:130434.

    Article  CAS  PubMed  Google Scholar 

  47. van Muijlwijk GH, Rice TA, Flavell RA, Palm NW, de Zoete MR. Allobaculum mucilyticum Sp. Nov. And Allobaculum fili Sp. Nov., isolated from the human intestinal tract. Int J Syst Evol Microbiol. 2023;73(1):1123.

    Google Scholar 

  48. Wu X, Chen H, Gao X, Gao H, He Q, Li G, Yao J, Liu Z. Natural herbal remedy Wumei Decoction ameliorates intestinal mucosal inflammation by inhibiting Th1/Th17 cell differentiation and maintaining microbial homeostasis. Inflamm Bowel Dis. 2022;28(7):1061–71.

    Article  PubMed  Google Scholar 

  49. Rengarajan S, Vivio EE, Parkes M, Peterson DA, Roberson E, Newberry RD, Ciorba MA, Hsieh CS. Dynamic Immunoglobulin responses to gut bacteria during inflammatory bowel disease. Gut Microbes. 2020;11(3):405–20.

    Article  PubMed  Google Scholar 

  50. Ren Z, Xu Z, Amakye WK, Liu W, Zhao Z, Gao L, Wang M, Ren J. Hericium erinaceus mycelium-derived polysaccharide alleviates ulcerative colitis and modulates gut microbiota in cynomolgus monkeys. Mol Nutr Food Res. 2023;67(3):e2200450.

    Article  PubMed  Google Scholar 

  51. Richter H, Gover O, Schwartz B. Anti-inflammatory activity of black soldier fly oil associated with modulation of TLR signaling: A metabolomic approach. Int J Mol Sci. 2023;24(13):10634.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Vitali R, Prioreschi C, Lorenzo Rebenaque L, Colantoni E, Giovannini D, Frusciante S, Diretto G, Marco-Jiménez F, Mancuso M, Casciati A, et al. Gut-brain axis: insights from hippocampal neurogenesis and brain tumor development in a mouse model of experimental colitis induced by dextran sodium sulfate. Int J Mol Sci. 2022;23(19):11495.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Wang X, Liang T, Mao Y, Li Z, Li X, Zhu X, Cao F, Zhang J. Nervonic acid improves liver inflammation in a mouse model of Parkinson’s disease by inhibiting Proinflammatory signaling pathways and regulating metabolic pathways. Phytomedicine. 2023;117:154911.

    Article  CAS  PubMed  Google Scholar 

  54. Lewkowicz N, Piątek P, Namiecińska M, Domowicz M, Bonikowski R, Szemraj J, Przygodzka P, Stasiołek M, Lewkowicz P. Naturally occurring nervonic acid ester improves Myelin synthesis by human oligodendrocytes. Cells. 2019;8(8):786.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Konstantynowicz-Nowicka K, Berk K, Chabowski A, Kasacka I, Bielawiec P, Łukaszuk B, Harasim-Symbor E. High-fat feeding in time-dependent manner affects metabolic routes leading to nervonic acid synthesis in NAFLD. Int J Mol Sci. 2019;20(15):3829.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Pegoraro NS, Camponogara C, Cruz L, Oliveira SM. Oleic acid exhibits an expressive anti-inflammatory effect in croton oil-induced irritant contact dermatitis without the occurrence of toxicological effects in mice. J Ethnopharmacol. 2021;267:113486.

    Article  CAS  PubMed  Google Scholar 

  57. Ben-Dror K, Birk R. Oleic acid ameliorates palmitic acid-induced ER stress and inflammation markers in Naive and cerulein-treated exocrine pancreas cells. Biosci Rep. 2019;39(5):BSR20190054.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Cao Y, Liu B, Li W, Geng F, Gao X, Yue L, Liu H, Liu C, Su Z, Lü J, et al. Protopanaxadiol manipulates gut microbiota to promote bone marrow hematopoiesis and enhance immunity in cyclophosphamide-induced immunosuppression mice. MedComm (2020). 2023;4(2):e222.

    Article  CAS  PubMed  Google Scholar 

  59. Jiang H, Horiuchi Y, Hironao KY, Kitakaze T, Yamashita Y, Ashida H. Prevention effect of Quercetin and its glycosides on obesity and hyperglycemia through activating AMPKα in high-fat diet-fed ICR mice. J Clin Biochem Nutr. 2020;67(1):74–83.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Moon N, Figgins B, Altshuler E, Pham A, Kamel AY. Concurrent zinc and vitamin B(6) deficiencies in acutely exacerbated inflammatory bowel disease: case reports. Nutr Clin Pract. 2022;37(1):203–8.

    Article  PubMed  Google Scholar 

  61. Xu D, Wu Q, Liu W, Hu G, Meng H, Wang J. Therapeutic efficacy and underlying mechanisms of Gastrodia Elata polysaccharides on dextran sulfate sodium-induced inflammatory bowel disease in mice: modulation of the gut microbiota and improvement of metabolic disorders. Int J Biol Macromol. 2023;248:125919.

    Article  CAS  PubMed  Google Scholar 

  62. Tamura M, Hoshi C, Hori S. Xylitol affects the intestinal microbiota and metabolism of Daidzein in adult male mice. Int J Mol Sci. 2013;14(12):23993–4007.

    Article  PubMed  PubMed Central  Google Scholar 

  63. He J, Li X, Yan M, Chen X, Sun C, Tan J, Song Y, Xu H, Wu L, Yang Z. Inulin reduces kidney damage in type 2 diabetic mice by decreasing inflammation and serum metabolomics. J Diabetes Res 2024, 2024:1222395.

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Acknowledgements

We would like to thank Associate Professor Shi Yingjuan from the School of Foreign Languages of Jiangsu University for her help in paper writing and language polishing.

Funding

This work was supported by Zhenjiang Key R&D Project-Social Development (SH2023073 and SH2022083), Jiangsu Province Traditional Chinese medicine science and technology development program (MS2022126).

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Author notes

  1. Peng Ma and Wen Sun contributed equally to this work.

Authors and Affiliations

  1. Department of Anesthesiology, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, 212001, China

    Peng Ma

  2. Department of Critical Care Medicine, Jurong Hospital Afliated to Jiangsu University, Zhenjiang, Jiangsu, 212400, China

    Wen Sun

  3. Department of Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, 212013, China

    Chang Sun, Jiajun Tan, Xueyun Dong, Asmaa Ali, Leilei Zhang & Liang Wu

  4. Health Testing Center, Zhenjiang Center for Disease Control and Prevention, Zhenjiang, 212002, China

    Jiayuan He

  5. Department of Pulmonary Medicine, Abbassia Chest Hospital, EMOH, Cairo, 11517, Egypt

    Asmaa Ali

  6. Public Experiment and Service Center, Jiangsu University, Zhenjiang, 212013, China

    Min Chen

  7. Department of Laboratory Medicine, Taizhou Second People’s Hospital, Taizhou, 225309, China

    Liang Wu & Pingping Wang

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Contributions

P M: Writing – review & editing, Writing – original draft, Methodology, Investigation, Formal analysis, Data curation. W S: Writing – review & editing, Methodology, Investigation, Data curation. C S: Writing – review & editing, Methodology, Investigation, Data curation. J T: Writing – original draft, Methodology. X D: Writing – original draft, Validation, Methodology. J H: Writing – review & editing, Resources, Methodology. A A: Writing – review & editing, Writing – original draft, Methodology, Formal analysis.M C: Methodology, Investigation, Data curation. L Z: Writing – original draft, Validation, Methodology, Funding acquisition, Data curation, Conceptualization. L W: Writing – review & editing, Writing – original draft, Validation, Supervision, Methodology, Funding acquisition, Data curation, Conceptualization. P W Writing – review & editing, Writing – original draft, Validation, Supervision, Methodology, Funding acquisition, Data curation, Conceptualization.

Corresponding authors

Correspondence to Liang Wu or Pingping Wang.

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Ethics approval and consent to participate

Relevant studies were conducted after approval by the Ethics Committee and the Experimental Animal Management and Use Committee of Jiangsu University (protocol code UJSIACUC-AP-2022032016). All methods were carried out following relevant guidelines and regulations.

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The authors declare no competing interests.

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Ma, P., Sun, W., Sun, C. et al. Using gut microbiota and non-targeted metabolomics techniques to study the effect of xylitol on alleviating DSS-induced inflammatory bowel disease in mice. BMC Immunol 26, 18 (2025). https://doiorg.publicaciones.saludcastillayleon.es/10.1186/s12865-025-00700-z

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BMC Immunology

ISSN: 1471-2172

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