Role of gut microbiota and mesenteric adipose tissue in the pathology of Crohn’s disease: Potential therapeutic targets

Abstract

This editorial comments on the article by Wu et al in the World Journal of Gastroenterology. The article explored the relationship between mesenteric adipose tissue, creeping fat, inflammation, and gut microbiota in Crohn’s disease (CD). We discussed three key aspects of the interaction between gut microbiota and inflammatory bowel disease (IBD): The physiological functions of the gut microbiota, the potential role of probiotics in IBD treatment; and the effect of fecal microbiota transplantation (FMT) in combating IBD. IBD, comprising CD and ulcerative colitis (UC), is influenced by the gut microbiota. Changes in gut microbiota composition disrupt intestinal function and promote chronic inflammation, but the exact mechanisms remain unclear. Probiotics have demonstrated some efficacy in inducing remission in UC, though their effectiveness in CD is still debated. FMT shows promise in treating IBD, especially UC, by restoring gut microbiota diversity and inducing clinical remission. As for CD, FMT has potential, but more studies are needed to confirm its long-term effectiveness and safety. Dietary approaches may help manage IBD symptoms or disease activity, but patient adherence is crucial. Clinicians and researchers must recognize the importance of the gut microbiota and the need for personalized therapies targeting microbial imbalances.

Key Words: Crohn’s disease; Gut microbiota; Probiotics; Ulcerative colitis; Inflammatory bowel disease

Core Tip: This editorial highlighted the role of the gut microbiota in inflammatory bowel disease (IBD), focusing on the potential of probiotics, fecal microbiota transplantation, and dietary strategies in managing IBD. The gut microbiota plays a crucial role in IBD. Probiotics show potential in ulcerative colitis, but further research is needed for Crohn’s disease. Fecal microbiota transplantation offers promise for ulcerative colitis, and personalized therapies targeting microbial imbalances may improve IBD management. Dietary approaches can aid in managing IBD symptoms, but patient adherence is essential. Clinicians and researchers should focus on the gut microbiota and personalized therapies for IBD.

INTRODUCTION

The interaction between the gut microbiota and inflammatory bowel disease (IBD) has long been discussed. In a recent study, Wu et al[1] investigated the relationship between mesenteric adipose tissue (MAT), creeping fat, inflammation, and the gut microbiota in Crohn’s disease (CD) in a mouse model. The authors reported that the gut microbiota plays a crucial role in CD pathology and that targeting MAT and creeping fat could offer therapeutic potential. IBD, which includes CD and ulcerative colitis (UC), is a condition marked by persistent inflammation of the intestines. In recent years, the global incidence and prevalence of IBD have been on the rise[2]. IBD is influenced by various environmental factors, such as diet, lifestyle, air pollution, and medical history, including medications, surgeries, and vaccines[3,4]. Additionally, IBD is closely related to genes and the gut microbiota. Changes in the gut microbiota can lead to intestinal dysfunction, which in turn causes chronic inflammation in the gut[5]. However, the exact pathogenesis by which these factors contribute to the disease is not fully understood, and it remains unclear which specific microbiota species are responsible for causing IBD. As a result, this area presents valuable opportunities for research, and future treatment approaches could potentially target the gut microbiota.

PHYSIOLOGICAL FUNCTIONS OF GUT MICROBIOTA AND ITS ASSOCIATION WITH DISEASES

The gut microbiota plays an important role in many physiological functions, including helping the digestive systems function properly, maintaining intestinal immunity, and communicating with the central nervous system via the gut-brain axis[6]. As a result, an imbalanced gut microbiota can lead to a wide range of diseases, including IBD, obesity, diabetes, and depression[6]. The gut microbiota can be influenced by many factors, including diet, stress, and illness[7]. Changes in the gut microbiota can lead to deteriorated intestinal epithelium and dysfunction of the intestinal immune system, which in turn can cause intestinal inflammation.

In the feces of IBD patients, we can observe a decline in both the biodiversity and stability of the gut microbiota compared to healthy individuals[8]. In the gut mucosal microbiota, a decline in biodiversity in the inflamed gut mucosa compared to the non-inflamed gut mucosa has been observed[8]. There is a notable rise in the presence of Fusobacterium and Escherichia coli, specifically adherent-invasive Escherichia coli strains, within the gut microbiota of patients with IBD when compared to healthy individuals[9,10]. In summary, it is known that IBD is related to a decline in gut microbiota biodiversity. However, it has not been established whether gut inflammation causes changes in the microbiota, or if changes in the microbiota lead to inflammation. This is an area that requires further research.

THE POTENTIAL OF PROBIOTICS IN THE TREATMENT OF IBD

Probiotics are live microorganisms that when consumed in an appropriate manner can provide positive health benefits to the human body[11]. Probiotic products may contain one or more selected microbial strains. The most common and extensively studied probiotic strains are Lactobacillus, Bifidobacterium, and Saccharomyces species[12]. Bifico, which contains Bifidobacterium longum, Lactobacillus acidophilus, and Enterococcus faecalis, was reported to have potential effects in suppressing proinflammatory responses and reducing the recurrence rate of IBD[13].

Similarly, current research indicates that VSL#3, which is composed of the Lactobacillus genus, three species of the Bifidobacterium genus, and Streptococcus thermophilus, could possibly induce and maintain remission in UC more quickly and effectively than a placebo[14]. However, the effects of VSL#3 on CD are still controversial, and it is currently uncertain whether probiotics are beneficial for CD. The effectiveness of probiotic treatment was reported to vary among patients, possibly due to genetic differences or other factors, and probiotics have not been established as a standard treatment for IBD to date. Furthermore, randomized controlled trials (RCT) are needed to identify which patients are more suitable for probiotic therapy.

POTENTIAL ROLE OF FECAL MICROBIOTA TRANSPLANTATION IN IBD TREATMENT

Fecal microbiota transplantation (FMT) involves stool transfer from a healthy donor into the intestines of a patient as a therapeutic approach for treating various diseases. Beneficial bacteria from the healthy donor’s feces help inhibit the growth of pathogenic bacteria in the patient, reduce inflammation, and restore the intestinal barrier function[15]. FMT is primarily used to treat Clostridium difficile infection, especially in cases of recurrent Clostridium difficile infection that do not respond to antibiotic treatment[16]. Additionally, a recent systematic review indicates that FMT can help manage obesity and metabolic syndrome by improving insulin sensitivity, although there is some variation in results across different studies[17]. FMT has also been reported to be potentially beneficial for controlling diseases closely related to the gut microbiota, such as irritable bowel syndrome[18,19].

Recently, researchers investigated whether FMT can induce remission of UC. Březina et al[20] reported that FMT could serve as a treatment option for UC, as it could induce clinical remission and increase the recipient’s gut microbiota diversity. Also, using oral administration for FMT could improve the clinical remission rate of UC[21]. In a Chinese randomized study, Fang et al[22] reported the long-term effects of FMT in the treatment of UC. Recent studies have shown that pathological evaluation of MAT and intestinal tissue from CD patients can reveal inflammation and fibrosis. CD can be assessed by pathological or imaging changes in MAT and can be treated by targeting the inflammation in MAT. These studies also suggested that FMT holds significant potential as a therapeutic approach for CD[1,23]. However, to date, the evidence on whether FMT can help to maintain remission of CD remains inconclusive. Additional large-scale studies are necessary to verify its long-term effectiveness and safety[24].

DIETARY STRATEGIES FOR IBD

Current research showed that the increasing incidence of IBD is associated with a rising prevalence of the Western diet[25]. The excessive intake of saturated fats and sugars promotes the growth of proinflammatory bacteria, such as Proteobacteria, and reduces beneficial bacteria, such as Firmicutes and Bifidobacteria. This imbalance disrupts gut homeostasis and increases inflammation[26,27]. Additionally, a high-fat diet can lead to intestinal barrier dysfunction, increasing intestinal permeability, and further exacerbating intestinal inflammation[28]. Several dietary strategies are currently considered effective for managing IBD, including the Mediterranean diet, low FODMAP diet, specific carbohydrate diet (SCD), exclusive enteral nutrition (EEN), and CD exclusion diet (CDED)[29-31].

A recent study showed that the Mediterranean diet helped reduce disease activity and inflammatory biomarkers in UC or CD patients, improving the quality of life for individuals with IBD[32]. Further well-designed RCTs are warranted to evaluate the effectiveness of the Mediterranean diet in managing IBD. However, the Mediterranean diet may pose challenges for IBD patients due to its high fiber content and the difficulty of digesting certain foods, particularly during active disease phases[33].

A low FODMAP diet, which restricts foods rich in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols, can help alleviate symptoms in individuals with IBD who have concomitant irritable bowel syndrome-like symptoms[34]. However, a low FODMAP diet cannot improve mucosal inflammation and may even cause an imbalance in the gut microbiota[35].

SCD, which emphasizes the exclusion of complex carbohydrates in favor of simple carbohydrates, seems to help reduce intestinal inflammation and gastrointestinal symptoms[36]. However, some experiments show that the SCD has limited effects on the symptoms of IBD patients, and therefore further well-designed RCTs are needed[37].

EEN is a first-line treatment for children with mild to moderate CD and uses a specialized formula that provides complete nutrition while alleviating intestinal inflammation and supporting growth and development[38]. EEN requires complete avoidance of solid foods, leading to low adherence and taste fatigue. To address this, the CDED was developed, which eliminates trigger foods like dairy, gluten, and processed meats while including gut-healing foods, such as legumes, fruits, and vegetables[39]. In children, the effectiveness of CDED combined with partial enteral nutrition has been experimentally validated[40]. For adults, a recent RCT demonstrated that CDED is effective in both inducing and maintaining remission in individuals with mild-to-moderate CD[41].

CONCLUSION

Targeting the gut microbiota, particularly through promising approaches such as probiotics, FMT, and dietary strategies, may be effective for treating IBD. While probiotics have shown some efficacy in UC, their effects in CD are less certain. FMT has been proven successful in both inducing and sustaining remission in UC; however, more research is required to establish its long-term safety and effectiveness in UC and CD. This underscores the potential for gut microbiota-focused therapies in IBD management. Using dietary approaches to manage IBD symptoms or disease activity may be feasible, but attention must be paid to patient adherence. Beyond the treatments already explored, it is important to investigate additional therapeutic alternatives. Rigorous research is crucial to assess their long-term effectiveness and confirm their potential to offer sustained benefits for patients.