Gut Flora Research Articles

A critical review on effects of artificial sweeteners on gut microbiota and gastrointestinal health.

Artificial sweeteners have emerged as popular alternatives to traditional sweeteners, driven by the growing concern over sugar consumption and its associated rise in obesity and metabolic disorders. Despite their widespread use, the safety and health implications of artificial sweeteners remain a topic of debate, with conflicting evidence contributing to uncertainty about their long-term effects. This review synthesizes current scientific evidence regarding the impact of artificial sweeteners on gut microbiota and gastrointestinal health. Our analysis of in vitro experiments, animal models, and clinical trials reveals that artificial sweeteners can alter the composition and abundance of gut microbes. These changes raise concerns about their potential to affect overall gut health and contribute to gastrointestinal disorders. Additionally, artificial sweeteners have been shown to influence the production of metabolites by gut bacteria, further impacting systemic health. The findings suggest that artificial sweeteners may have complex and sometimes contradictory effects on gut microbiota. While some studies indicate potential benefits, such as reduced caloric intake and weight management, others highlight detrimental effects on microbial balance and metabolic functions. The inconsistent results underscore the need for further research to comprehensively understand the physiological impacts of various artificial sweeteners on human health. Future studies should aim for long-term, well-controlled investigations to clarify these relationships, ensuring evidence-based guidelines for the safe use of artificial sweeteners in diet management. © 2025 Society of Chemical Industry.

Human-derived microRNA 21 regulates indole and L-tryptophan biosynthesis transcripts in the gut commensal Bacteroides thetaiotaomicron.

The mammalian gut represents one of the largest and most dynamic host-microbe interfaces. Host-derived microRNAs (miRNAs), released from the gut epithelium into the lumen, have emerged as important contributors to host-microbe crosstalk. Levels of several miRNAs are altered in the stool of patients with irritable bowel syndrome or inflammatory bowel disease. Understanding how miRNAs interact with and shape gut microbiota function is crucial as it may enable the development of new targeted treatments for intestinal diseases. This study provides evidence that the miRNA miR-21 can rapidly associate with diverse microbial cells form the gut and increase levels of transcripts involved in tryptophan synthesis in a ubiquitous gut microbe. Tryptophan catabolites regulate key functions, such as gut immune response or permeability. Therefore, this mechanism represents an unexpected host-microbe interaction and suggests that host-derived miR-21 may help regulate gut function via the gut microbiota.

Interactions between gut microbes and host promote degradation of various fiber components in Meishan pigs.

Studies on porcine intestinal microbiota have been widely conducted, and some microbial taxa with fiber degradation functions have been identified. However, the mechanisms of division among gut microbes in the degradation of complex fiber components are still unclear. In addition, the regulation of fiber digestion by host through absorption of short-chain fatty acids (SCFAs) needs to be further investigated. Our study used apparent total tract digestibility of dietary fiber to assess the utilization efficiency of dietary fiber between Meishan and Large White pigs. Subsequently, through metagenome sequencing and determination of fiber-degrading products, we found that in Meishan pigs, positive interactions among Treponema bryantii, Treponema sp., Rikenellaceae bacterium, and Bacteroidales bacterium WCE2004 facilitated the degradation of both cellulose and pectin. RNA-seq analysis elucidated breed-specific genes associated with SCFA absorption in cecum. By integrating multi-omics data, we constructed a framework outlining host-microbiota interactions that control dietary fiber utilization in pigs. Our data provide novel insights into host-microbiota interactions regulating fiber degradation and lay some theoretical foundations for improving the utilization efficiency of high-fiber cereal feed in pigs through targeted modulation of gut microbial function.

Convergent evolution of oxidized sugar metabolism in commensal and pathogenic microbes in the inflamed gut

Inflammation-associated perturbations of the gut microbiome are well characterized, but poorly understood. Here, we demonstrate that disparate taxa recapitulate the metabolism of the oxidized sugars glucarate and galactarate, utilizing enzymatically divergent, yet functionally equivalent, gud/gar pathways. The divergent pathway in commensals includes a putative 5-KDG aldolase (GudL) and an uncharacterized ABC transporter (GarABC) that recapitulate the function of their non-homologous counterparts in pathogens. A systematic bioinformatic search for the gud/gar pathway in gut microbes identified 887 species putatively capable of metabolizing oxidized sugars. Previous studies showed that inflammation-derived nitrate, formed by nitric oxide reacting with superoxide, promotes pathogen growth. Our findings reveal a parallel phenomenon: oxidized sugars, also produced from reactions with nitric oxide, serve as alternative carbon sources for commensal microbes. Previously considered a pathogen virulence factor, oxidized sugar metabolism is also present in specific commensals and may contribute to their increased relative abundance in gastrointestinal inflammation.

Deciphering the therapeutic effects of Xiyanping injection: insights into pulmonary and gut microbiome modulation, SerpinB2/PAI-2 targeting, and alleviation of influenza a virus-induced lung injury

Infection with Influenza A virus (IAV) induces severe inflammatory responses and lung injury, contributing significantly to mortality and morbidity rates. Alterations in the microbial composition of the lungs and intestinal tract resulting from infection could influence disease progression and treatment outcomes. Xiyanping (XYP) injection has demonstrated efficacy in clinical treatment across various viral infections. However, its specific effects and mechanisms against IAV remain unclear. In this study, we established an IAV infection mice model, and utilized 16 S rRNA sequencing, RNA sequencing, protein chips, and molecular docking, to investigate the mechanisms of XYP injection on altering pulmonary and gut microbiota, and identifying its target sites. We revealed that XYP injection significantly reduced mortality, weight loss, lung viral titers, and lung pathology in IAV-infected mice. XYP injection down-regulated the activity of malondialdehyde, and the levels of interleukin (IL)-1β, IL-5, IL-6, tumor necrosis factor-α, IL-18, IL-15, granulocyte colony-stimulating factor, IL-9, chemokine (C-C motif) ligand-5, and C-X-C motif chemokine ligand 5, while up-regulated the activities of glutathione peroxidase reactive and superoxide dismutase, and the level of interferon-γ. The diversity of the pulmonary and gut microbiota was altered slightly after XYP injection. The linear discriminant analysis of the gut microbes revealed a higher proportion of potentially beneficial bacteria, including Akkermansia, Parabacteroides goldsteinii, Defluviitaleaceae, Oscillospirales, and Eubacterium_coprostanoligenes_group characterized the XYP group. Peritoneal macrophage RNA sequencing highlighted Serpinb2 as the most significantly regulated gene by XYP injection, along with consistent changes in multiple downstream Th2 structure genes. KEGG pathway analysis indicated significant modifications in genes associated with influenza A, mitogen-activated protein kinase signaling, nuclear factor kappa-B signaling, and apoptosis following XYP injection. Finally, human protein chips and molecular docking were carried out to confirm the binding of the main component of XYP injection, andrographolide, with SERPINB2/PAI-2 protein. Overall, our study provides valuable insights into the therapeutic potential of XYP injection in treating influenza, highlighting its multifaceted effects on host microbiota and immune responses, and pinpointing SerpinB2/PAI-2 as the target for XYP injection in exerting anti-inflammatory and antiviral therapeutic mechanisms.

Environmental and population influences on mummichog (Fundulus heteroclitus) gut microbiomes.

The mummichog fish, a common resident of North America's east coast estuaries, has evolved the ability to survive in waters contaminated with toxic chemicals that would typically be deadly. Our study investigates how living in and adapting to these toxic environments may affect their gut microbiomes. We compared mummichogs from a polluted area in Massachusetts with those from a non-polluted site and found significant differences in their gut microbes. Interestingly, when we raised the next generation of these fish in a lab, these differences disappeared, suggesting that the environment plays a more crucial role in shaping the gut microbiome than genetics. Understanding these changes helps shed light on how animals and their associated microbiomes adapt to pollution, which can inform conservation efforts and our broader understanding of environmental impacts on host-microbe dynamics.

Role of Crosstalk Between Gut Microbiota and Immune Cells in Colorectal Cancer: A Narrative Review

Abstract Colorectal cancer (CRC) ranks among the most prevalent and deadly cancers globally, with its incidence increasing due to lifestyle factors such as increased consumption of red meat and decreased vegetable intake. A distinctive aspect of CRC is its strong connection to the gut microbiota, which is crucial in both tumorigenesis and immune regulation. This narrative review provides a comprehensive analysis of the interactions between gut microbiota and the immune system, focusing on their importance in CRC progression and responses to immunotherapy. Imbalances in the composition of gut microbes are strongly associated with CRC development. Notably, species such as Fusobacterium nucleatum and Bacteroides fragilis have been identified as key regulators of immune responses within the tumor microenvironment. These microbes affect the functions of immune cells, such as T cells, macrophages and myeloid-derived suppressor cells, thereby influencing cancer progression and prognosis. Additionally, this review underscores the potential of gut microbiota as biomarkers for CRC detection and outcome prediction. There is also growing interest in the use of probiotics, fecal microbiota transplantation and dietary modifications as supplementary treatments. A deeper understanding of how microbial communities interact with the immune system may pave the way for novel personalized therapies, particularly by enhancing the effectiveness of immune checkpoint inhibitors.

Gut microbes associated with functional cure of chronic hepatitis B.

Hepatitis B virus (HBV) is prevalent worldwide and is difficult to eradicate. Current treatment strategies for chronic hepatitis B ultimately seek to achieve functional cure (FC); however, the factors contributing to FC remain unclear. We aimed to investigate the gut microbiota profiles of patients with chronic hepatitis B who achieved FC. Among 105 HBeAg-negative patients with chronic hepatitis B, 70 were enrolled, after excluding patients with cirrhosis or hepatocellular carcinoma and those receiving nucleoside analogs. The gut microbiota of patients who achieved FC was assessed and compared with that of patients with high-titer of HBV DNA (HBV DNA ≥ 3.3 log IU/mL) or low-titer of HBV DNA (HBV DNA < 3.3 log IU/mL). Furthermore, we used cell culture-generated HBV (HBVcc) as a model for HBV infection to evaluate the effects of short-chain fatty acids (SCFAs) produced by the identified bacteria. There was no difference in the alpha or beta diversity of the gut microbiota between the FC group and the other groups. However, compared with the other groups, the FC group presented a greater relative abundance of bacteria that produce SCFAs, especially butyrate. In vitro studies demonstrated that 1.0mM butyrate reduces HBsAg production in HBVcc-infected cells. Furthermore, butyrate administration was most effective at the post-HBV infection stage. Our findings suggest that butyrate-producing bacteria contribute to FC in HBeAg-negative patients with chronic hepatitis B through butyrate-mediated inhibition of HBV production.

Motility genes are associated with the occurrence of Drosophila melanogaster-associated gut microbes

Abstract Recent work highlighted the role of motility genes in dispersing fly-associated microbes and their spread between hosts. We investigated whether bacterial genes encoding motility are associated with the occurrence of bacteria above passive dispersal levels in the gut of wild Drosophila melanogaster. We revisited 16S amplicon and shotgun metagenome data of wild flies and correlated four genera of bacteria (Commensalibacter, Gluconobacter, Lactobacillus, and Tatumella) with motility genes. We plotted the microbes against neutral models of ecological drift and passive dispersal. Microbes with positive correlations to motility were exclusively found at or above neutral model predictions, suggesting motility genes are crucial for fly microbiota spread and colonization. This information is crucial for understanding how specific gene functions contribute to microbial community dispersal and colonization within the fly host. Moreover, this study’s findings serve as a proof of concept for using the neutral model to predict microbial functions essential for survival and dissemination in diverse hosts.

Exploring the potential of homologous epitopes from gut microbes for SARS-CoV-2 vaccine design, using molecular modelling to gain critical insights

Exploring the potential of homologous epitopes from gut microbes for SARS-CoV-2 vaccine design, using molecular modelling to gain critical insights

The Crucial Role of Gut Microbiome in Cardiovascular Health

Madam, The intestinal microbiome refers to the vast assortment of tiny organisms in the human digestive tract. These bacteria support the body's physiological processes and biochemical responses via the compounds they generate. Research suggests that variations in gut microbiota may influence a variety of human health disorders, notably those involving the heart. Recent studies have shown that changes in the types and activities of bacteria in the intestines, known as gut microflora dysbiosis, can hasten the course of cardiovascular illnesses 1. Another research also tied gut microbiota to heart disease, but this time by demonstrating how metabolites like trimethylamine N-oxide (TMAO) will increase risk, indicating that dietary and probiotic strategies could be used for remedy 2. A recent study from April 2024 identified Oscillibacter and Eubacterium as synergistic cholesterol metabolisers. The intermediate products that these bacteria form while converting cholesterol are finally degraded by other bacteria and flushed out from the body, reducing gut cholesterol and modulating the host's biochemical pathways, hence reducing both faecal and plasma cholesterol levels. The results may serve to facilitate novel potential interventions, for example targeting the microbiome in cardiovascular disease (CVD) treatment 3. A novel association was observed that higher serum C-reactive protein (CRP) levels correlate with Parabacteroides merdae and unclassified Firmicutes strongly associate with plasma cholesterol. As for Firmicutes a well-defined metagenomic species pangenome (MSP) from this phylum, termed msp_120, was found to be associated with higher cholesterol levels that indicate its role in cholesterol metabolism and thus possibly also as a determinant of cardiovascular disease risk factors concerning high serum-cholesterol level. This finding reveals a beholden link between the gut microbiome and systemic inflammation with CVD 3. In Pakistan, where CVDs are a major health concern, there is a significant research gap regarding the local gut microbiome's role in CVD. We conducted thorough research on PubMed and found no original research articles studying the relationship of gut microbiome with CVD except for a few review articles 4 and 5; this is indicative of the lack of attention to this topic in Pakistan. It is important to perform ethnic-specific studies for these unique interactions in the Pakistani population. Research in this direction may point out the specific role of gut microbiota so probiotic interventions and dietary recommendations can be used to improve cardiovascular health in the Pakistani population.

Early-Life Antibiotic Exposures: Paving the Pathway for Dysbiosis-Induced Disorders.

Microbiota encompasses a diverse array of microorganisms inhabiting specific ecological niches. Gut microbiota significantly influences physiological processes, including gastrointestinal motor function, neuroendocrine signalling, and immune regulation. They play a crucial role in modulating the central nervous system and bolstering body defence mechanisms by influencing the proliferation and differentiation of innate and adaptive immune cells. Given the potential consequences of antibiotic therapy on gut microbiota equilibrium, there is a need for prudent antibiotic use to mitigate associated risks. Observational studies have linked increased antibiotic usage to various pathogenic conditions, including obesity, inflammatory bowel disease, anxiety-like effects, asthma, and pulmonary carcinogenesis. Addressing dysbiosis incidence requires proactive measures, including prophylactic use of β-lactamase drugs (SYN-004, SYN-006, and SYN-007), hydrolysing the β-lactam in the proximal GIT for maintaining intestinal flora homeostasis. Prebiotic and probiotic supplementations are crucial in restoring intestinal flora equilibrium by competing with pathogenic bacteria for nutritional resources and adhesion sites, reducing luminal pH, neutralising toxins, and producing antimicrobial agents. Faecal microbiota transplantation (FMT) shows promise in restoring gut microbiota composition. Rational antibiotic use is essential to preserve microflora and improve patient compliance with antibiotic regimens by mitigating associated side effects. Given the significant implications on gut microbiota composition, concerted intervention strategies must be pursued to rectify and reverse the occurrence of antibiotic-induced dysbiosis. Here, antibiotics-induced microbiota dysbiosis mechanisms and their systemic implications are reviewed. Moreover, proposed interventions to mitigate the impact on gut microflora are also discussed herein.

Interactions between the tumor microbiota and breast cancer

Breast cancer is the most common malignancy in women worldwide. Changes in the microbiota and their metabolites affect the occurrence and development of breast cancer; however, the specific mechanisms are not clear. Gut microbes and their metabolites influence the development of breast cancer by regulating the tumor immune response, estrogen metabolism, chemotherapy, and immunotherapy effects. It was previously thought that there were no microorganisms in breast tissue, but it is now thought that there are microorganisms in breast cancer that can affect the outcome of the disease. This review builds on existing research to comprehensively analyze the role of gut and intratumoral microbiota and their metabolites in the development and metastasis of breast cancer. We also explore the potential function of the microbiota as biomarkers for prognosis and therapeutic response, highlighting the need for further research to clarify the causal relationship between the microbiota and breast cancer. We hope to provide new ideas and directions for the development of new methods for breast cancer treatment.

Gut Microbes as the Major Drivers of Rheumatoid Arthritis: Our Microbes Are Our Fortune!

Rheumatoid arthritis (RA) is an autoimmune disease with an unknown etiology. While certain genes provide strong susceptibility factors, the role of environmental factors is becoming increasingly recognized. Among genetic factors, human leukocyte antigen (HLA) genes, encoded within the major histocompatibility complex (MHC), have been linked to predisposition to RA, while among environmental factors, smoking, infections and diet are the major contributors. Genetic and environmental factors impact microbial composition in the host. Based on the dysbiosis observed in the gut and lung microbiome, a mucosal origin of RA has been suggested. However, proving whether genes or microbes provide a stronger risk factor has been difficult. Studies from RA patients and various mouse models, specifically humanized mice expressing HLA class II genes, have been instrumental in defining the role of environmental factors such as smoking and endogenous small intestinal microbes in modulating arthritis severity. The consensus based on most studies support an interaction between host genetic and environmental factors in the onset and severity of disease. However, until now, no microbial markers for disease prognosis or treatment efficacy have been available. Here, the role of gut microbes as markers of disease severity, and the potential for using endogenous commensals for modulating immune responses to suppress inflammation in the context of genetic factors, are discussed.

Gut microbiota and quantitative traits divergence at different altitude of long-tailed dwarf hamsters, Cricetulus longicaudatus

To investigate the community structure and diversity of gut microflora and their function in body mass regulation, as well as the effects of various locations on gut microbiota and Cricetulus longicaudatus body mass regulation at various elevations. We examined the diversity, abundance, and community structure of the gut microbiota of long-tailed dwarf hamsters from eight regions in Shanxi province during summer using 16S rDNA sequencing technology and analyzed the relationships between these microbiota and environmental variables as well as morphological indicators. The results revealed Firmicutes and Bacteroidetes as the dominant phyla at the phylum level, with Lactobacillus emerging as the predominant genus. We observed differences of gut microflora between different areas, and this diversity is affected by altitude. The high-altitude areas individuals had lower β diversity of gut microbiota than the low-altitude area. Moreover, the body and skull indexes of long-tailed dwarf hamsters also changed with altitude. The result presented in this study indicated that the body size of long-tailed dwarf hamsters conforms to Bergmann's law. And Providencia had significant correlation with body size. Finally, functional analysis of the gut microbiota showed changes in metabolic function that depended on elevation, and collinear network analysis showed how the gut microbiota interacts with each other. All of these results suggest that long-tailed hamsters are different depending on their altitude, with altitude being the main factor affecting both the structure of microbes and the way their metabolism works. This study shows that altitude has a big effect on the gut microbiota and phenotypic traits of long-tailed hamsters. It also shows how well this species can adapt to changes in altitude.

Shenmai injection revives cardiac function in rats with hypertensive heart failure: involvement of microbial-host co-metabolism

Heart failure (HF) is a complex syndrome marked by considerable expenditures and elevated mortality and morbidity rates globally. Shenmai injection (SMI), a form of Traditional Chinese Medicine-based therapy, has demonstrated effectiveness in treating HF. Recent research suggests that Traditional Chinese Medicine (TCM) may induce beneficial changes in microbial-host co-metabolism, potentially providing cardiovascular protection. This study used a rat model of hypertensive heart failure (H-HF) to explore the mechanism of SMI. The possible compounds and key targets of SMI against H-HF were investigated using network pharmacology. The pharmacodynamics of SMI were validated using the H-HF animal model, with analysis of fecal gut microbiota integrating metabolomics and 16S rRNA sequencing. Metorigin metabolite traceability analysis and the MetaboAnalyst platform were utilized to explore the action mechanism. To evaluate changes in serum TMAO levels, targeted metabolomics was performed. Finally, the study looked at the intrinsic relationships among modifications in the intestinal flora, metabolite profile changes, and the targets of SMI compounds to clarify how they might be used to treat H-HF. According to metabolomics and 16S rRNA sequencing, by reestablishing homeostasis in the gut microbiota, SMI affects vital metabolic pathways, such as energy metabolism, amino acid metabolism, and bile acid metabolism. Increased serum TMAO levels were identified to be a risk factor for H-HF, and SMI was able to downregulate the levels of TMAO-related metabolites. Network pharmacology analysis identified 13 active components of SMI targeting 46 proteins, resulting in differential expression changes in 8 metabolites and 24 gut microbes. In conclusion, this study highlights the effectiveness of SMI in alleviating H-HF and its potential to modulate microbial-host co-metabolism. Through a comprehensive discussion of the interconnected relationships among the components, targets, metabolites, and gut microbiota, it provided fresh light on the therapeutic mechanism of SMI on H-HF.

I "Gut" Rhythm: the microbiota as a modulator of the stress response and circadian rhythms.

Modern habits are becoming more and more disruptive to health. As our days are often filled with circadian disruption and stress exposures, we need to understand how our responses to these external stimuli are shaped and how their mediators can be targeted to promote health. A growing body of research demonstrates the role of the gut microbiota in influencing brain function and behavior. The stress response and circadian rhythms, which are essential to maintaining appropriate responses to the environment, are known to be impacted by the gut microbiota. Gut microbes have been shown to alter the host's response to stress and modulate circadian rhythmicity. Although studies demonstrated strong links between the gut microbiota, circadian rhythms and the stress response, such studies were conducted in an independent manner not conducive to understanding the interface between these factors. Due to the interconnected nature of the stress response and circadian rhythms, in this review we explore how the gut microbiota may play a role in regulating the integration of stress and circadian signals in mammals and the consequences for brain health and disease.

Inference of the demographic histories and selective effects of human gut commensal microbiota over the course of human history.

Despite the importance of gut commensal microbiota to human health, there is little knowledge about their evolutionary histories, including their demographic histories and distributions of fitness effects (DFE) of mutations. Here, we infer the demographic histories and DFEs for amino-acid changing mutations of 39 of the most prevalent and abundant commensal gut microbial species found in Westernized individuals over timescales exceeding human generations. Some species display contractions in population size and others expansions, with several of these events coinciding with several key historical moments in human history. DFEs across species vary from highly to mildly deleterious, with differences between accessory and core gene DFEs largely driven by genetic drift. Within genera, DFEs tend to be more congruent, reflective of underlying phylogenetic relationships. Together, these findings suggest that gut microbes have distinct demographic and selective histories.

Taurochenodeoxycholic Acid Improves Growth, Physiology, Intestinal Microbiota, and Muscle Development in Red Swamp Crayfish (Procambarus clarkii)

Taurochenodeoxycholic acid (TCDCA), one of the bile acids, is thought to be involved in the regulation of muscle nutrient metabolism and gut microbial homeostasis. However, the effect of dietary addition of TCDCA on Procambarus clarkii is unclear. Therefore, in this study, an 8-week feeding experiment was conducted to explore the potential regulatory mechanisms of TCDCA on P. clarkii growth, physiology, muscle quality and gut microbes. The results indicated that dietary addition of TCDCA not only improved growth performance (final weight; weight gain; and specific growth rate) but also increased muscle elasticity and protein content. In addition, dietary TCDCA promotes muscle growth and development by increasing myofiber length, which is consistent with the activation of the expression of genes related to protein utilization (TOR and AKT) and muscle proliferation and differentiation (MyHC, MLC1, MEF2A, MEF2B). Importantly, 16s rRNA sequencing demonstrated that dietary TCDCA had no significant effect on gut microbial composition (alpha diversity) but significantly increased microbial abundance at the genus level. Functional prediction analysis of differential microbes revealed that dietary TCDCA may promote metabolism by altering gut microbes, thereby promoting muscle quality. In conclusion, our study demonstrates that the dietary addition of TCDCA promotes P. clarkii growth and muscle quality and protein deposition by altering gut microbes.

Lentinan's effect on gut microbiota and inflammatory cytokines in 5-FU-induced mucositis mice

Chemotherapeutic therapies for cancer are frequently associated with cytotoxic side effects that can be harmful to human health, including the development of intestinal mucositis (IM). It mostly affects the gastrointestinal tract, causing ulceration, inflammation, and the formation of lesions in the colon. Surprisingly, despite the frequency of IM, therapeutic choices remain restricted. In our search for new intestinal mucositis therapies, we wanted to see how Lentinan (LT), derived from Lentinus edodes, would fare in mouse models of intestinal mucositis. To create the intestinal mucositis model in mice, we gave them intra-peritoneal doses of 5-fluorouracil (5-FU) (50 mg/kg) and then tested the effects of Lentinan on intestinal mucositis. This examination required constant monitoring of several factors, such as body weight fluctuations, food consumption, and diarrhea. In addition, we measured the levels of certain inflammatory cytokines (Tumour Necrosis Factor-alpha (TNF-α), Interleukin-1 (IL-1), Interleukin-6 (IL-6), and Interleukin-10 (IL-10), looked at the expression of tight junction proteins (Zonula Occludens-1(ZO-1), Claudin-1), measured mucin-2 levels, and looked into changes in the gut flora. In the mouse model of intestinal mucositis, our findings showed that LT effectively reduced weight loss, increased food intake, and relieved diarrhea. Concurrently, we saw a decrease in the expression of inflammatory cytokines such as TNF-α, IL-1, and IL-6, as well as a considerable increase in the concentration of IL-10. Furthermore, LT reduced intestinal mucositis by increasing the length and structural integrity of the colon. Furthermore, increased expression of tight junction proteins (ZO-1, Claudin-1), mucin-2, and an increase in the number of goblet cells all confirmed our previous findings. Notably, the makeup of beneficial bacteria in the stomach increased as well. Finally, our findings suggest that LT can effectively prevent 5-fluorouracil-induced intestinal mucositis in mice by improving immune function, restoring intestinal barrier integrity, and rebalancing gut microbial flora.