Intestinal Homeostasis Research Articles

From Bacillus subtilis enhances immune response and contributes to the maintenance of intestinal microbial homeostasis.

The potential of surfactin as a microbial surfactant extends beyond its surfactant properties, impacting immune regulation and gut health. As the need for alternatives to traditional antibiotics continues to grow, surfactin's ability to enhance host defense mechanisms against common pathogens without directly targeting them with antibiotics offers a strategic advantage. Understanding how surfactin shapes the immune landscape and the gut microbiome can inform innovative interventions against immunosuppression and intestinal impairment, particularly in contexts such as cyclophosphamide-induced toxicity.

Multi-omics analyses of Bacillus amyloliquefaciens treated mice infected with Schistosoma japonicum reveal dynamics change of intestinal microbiome and its associations with host metabolism.

Schistosomiasis japonica is a serious threat to human health. It causes damage to the intestine and liver. Probiotic therapy has been shown to be effective in alleviating intestinal diseases and improving host health. Previous studies have found that Bacillus amyloliquefaciens could alleviate the pathological symptoms of schistosomiasis japonica, but the regulatory mechanism of alleviating schistosomiasis japonica is still unknown. This study analyzed the dynamic changes of intestinal microbiome in mice infected with Schistosoma japonicum after the intervention of B. amyloliquefaciens and its connection to host metabolism by multi-omics sequencing technology. B. amyloliquefaciens was found to significantly regulate the homeostasis of intestinal microbiota by promoting the growth of beneficial bacteria and inhibiting potential pathogenic bacteria and protect the number of core microbes. Meanwhile, the genes related to the metabolism of glycerophospholipids and amino acid from intestinal microbiome changed significantly, and were shown to be significantly positively correlated with the associated metabolites of microbial origin. Moreover, host metabolism (lipid metabolism and steroid hormone biosynthesis) was also found to be significantly regulated. The recovery of intestinal microbial homeostasis and the regulation of host metabolism revealed the potential probiotic properties of B. amyloliquefaciens, which also provided new ideas for the prevention and adjuvant treatment of schistosomiasis japonica.

Irisin promotes intestinal epithelial cell proliferation via Wnt/β-catenin and focal adhesion kinase signaling pathways

The regeneration of epithelia is crucial for maintaining intestinal homeostasis. Irisin is an exercise-induced hormone originally found to be secreted by skeletal muscles, thereby regulating energy metabolism. Recent studies have revealed that irisin protected against gut inflammation. However, the direct effects of irisin on the intestinal epithelial cells remain to be elucidated. In this study, mouse intestinal organoids were used to assess the effects of irisin on the proliferation of the intestinal epithelial cells. At a concentration of 100 ng/mL irisin significantly increased the growth of the intestinal organoids and upregulated the Wnt/β-catenin and focal adhesion kinase (FAK) signaling pathway genes. Notably, a FAK inhibitor 14 blocked the effects of irisin on the proliferation of the intestinal epithelial cells by inhibiting FAK phosphorylation, as well as the expressions of Wnt target genes. Furthermore, irisin (100 ng/mL) improved the recovery of the intestinal organoids from cellular damages caused by TNF-α, and markedly increased the expression of Wnt target genes in the intestinal epithelial cells. Taken together, irisin activates Wnt/β-catenin and FAK signaling pathways in the intestinal epithelial cells, thereby promoting intestinal epithelial self-renewal under normal homeostatic conditions and intestinal epithelial regeneration upon damages.

Oral Administration of Bioactive Nanoparticulates for Inflammatory Bowel Disease Therapy by Mitigating Oxidative Stress and Restoring Intestinal Microbiota Homeostasis.

The management of inflammatory bowel disease (IBD) continues to pose significant challenges due to the absence of curative therapies and a high rate of recurrence. Therefore, it is imperative to explore novel approaches to enhance the efficacy of IBD therapy. Herein, a bioactive nanoparticulate s is tailored designed to achieve a "Pull-Push" approach for efficient and safe IBD treatment by integrating reactive oxygen species (ROS) scavenging (Pull) with anti-inflammatory agent delivery (Push) in the inflammatory microenvironment. The multifunctional nanomedicine, designated MON-PAMAM@SASP, is developed through the encapsulation of sulfasalazine (SASP), a widely utilized clinical drug for the treatment of IBD, within cationic diselenide-bridged mesoporous organosilica nanoparticles (MONs) that possess significant antioxidant properties. Herein, poly(amidoamine) (PAMAM) endows the original MONs with positive charge characteristics. The MON-PAMAM@SASP not only displays the remarkable capability of neutralizing ROS to ameliorates intestinal damage, but also achieves controllable release of SASP to mitigate intestinal inflammation. Consequently, this nanomedicine effectively mitigates IBD by colitis in mouse models, and our current research has not identified any significant drug toxicity. Beyond regulating inflammatory microenvironment in intestine, treatment with MON-PAMAM@SASP results in increased richness and restores intestinal microbiota homeostasis, thereby mitigating IBD to a certain extent. Together, our work provides a highly versatile "Pull-Push" approach for IBD management and encourages the development of similar nanomedicine to treating multiple inflammatory diseases of gastrointestinal tract.

Candida tropicalis-derived vitamin B3 exerts protective effects against intestinal inflammation by promoting IL-17A/IL-22-dependent epithelial barrier function

ABSTRACT Candida tropicalis-a prevalent gut commensal fungus in healthy individuals – contributes to intestinal health and disease. However, how commensal C. tropicalis influences intestinal homeostasis and barrier function is poorly understood. Here, we demonstrated that the reference strain of C. tropicalis (MYA-3404) ameliorated intestinal inflammation in murine models of chemically induced colitis and bacterial infection. Intestinal colonization of C. tropicalis robustly upregulated the expression of IL-17A and IL-22 to increase barrier function and promote proliferation of intestinal epithelial cells in the mouse colon. Metabolomics analysis of fecal samples from mice colonized with C. tropicalis revealed alterations in vitamin B3 metabolism, promoting conversion of nicotinamide to nicotinic acid. Although nicotinamide worsened colitis, treatment with nicotinic acid alleviated disease symptoms and enhanced epithelial proliferation and Th17 cell differentiation. Oral gavage of C. tropicalis mitigated nicotinamide-induced intestinal dysfunction in experimental colitis. Blockade of nicotinic acid production with nicotinamidase inhibitors lowered the protective effects against colitis in mice treated with C. tropicalis. Notably, a clinical C. tropicalis strain isolated from patients with candidemia lacked the protective effects against murine colitis observed with the reference strain. Together, our results highlight a novel role for C. tropicalis in resolving intestinal inflammation through the modulation of vitamin B3 metabolism.

Metabolic regulation of intestinal homeostasis: molecular and cellular mechanisms and diseases.

Metabolism serves not only as the organism's energy source but also yields metabolites crucial for maintaining tissue homeostasis and overall health. Intestinal stem cells (ISCs) maintain intestinal homeostasis through continuous self-renewal and differentiation divisions. The intricate relationship between metabolic pathways and intestinal homeostasis underscores their crucial interplay. Metabolic pathways have been shown to directly regulate ISC self-renewal and influence ISC fate decisions under homeostatic conditions, but the cellular and molecular mechanisms remain incompletely understood. Understanding the intricate involvement of various pathways in maintaining intestinal homeostasis holds promise for devising innovative strategies to address intestinal diseases. Here, we provide a comprehensive review of recent advances in the regulation of intestinal homeostasis. We describe the regulation of intestinal homeostasis from multiple perspectives, including the regulation of intestinal epithelial cells, the regulation of the tissue microenvironment, and the key role of nutrient metabolism. We highlight the regulation of intestinal homeostasis and ISC by nutrient metabolism. This review provides a multifaceted perspective on how intestinal homeostasis is regulated and provides ideas for intestinal diseases and repair of intestinal damage.

Host-pathobiont interactions in Crohn's disease.

The mammalian intestine is colonized by trillions of microorganisms that are collectively referred to as the gut microbiota. The majority of symbionts have co-evolved with their host in a mutualistic relationship that benefits both. Under certain conditions, such as in Crohn's disease, a subtype of inflammatory bowel disease, some symbionts bloom to cause disease in genetically susceptible hosts. Although the identity and function of disease-causing microorganisms or pathobionts in Crohn's disease remain largely unknown, mounting evidence from animal models suggests that pathobionts triggering Crohn's disease-like colitis inhabit certain niches and penetrate the intestinal tissue to trigger inflammation. In this Review, we discuss the distinct niches occupied by intestinal symbionts and the evidence that pathobionts triggering Crohn's disease live in the mucus layer or near the intestinal epithelium. We also discuss how Crohn's disease-associated mutations in the host disrupt intestinal homeostasis by promoting the penetration and accumulation of pathobionts in the intestinal tissue. Finally, we discuss the potential role of microbiome-based interventions in precision therapeutic strategies for the treatment of Crohn's disease.

The dynamic crosslinking between gut microbiota and inflammation during aging: reviewing the nutritional and hormetic approaches against dysbiosis and inflammaging.

The early-life gut microbiota (GM) is increasingly recognized for its contributions to human health and disease over time. Microbiota composition, influenced by factors like race, geography, lifestyle, and individual differences, is subject to change. The GM serves dual roles, defending against pathogens and shaping the host immune system. Disruptions in microbial composition can lead to immune dysregulation, impacting defense mechanisms. Additionally, GM aids digestion, releasing nutrients and influencing physiological systems like the liver, brain, and endocrine system through microbial metabolites. Dysbiosis disrupts intestinal homeostasis, contributing to age-related diseases. Recent studies are elucidating the bacterial species that characterize a healthy microbiota, defining what constitutes a 'healthy' colonic microbiota. The present review article focuses on the importance of microbiome composition for the development of homeostasis and the roles of GM during aging and the age-related diseases caused by the alteration in gut microbial communities. This article might also help the readers to find treatments targeting GM for the prevention of various diseases linked to it effectively.

Pyroptosis regulation by Salmonella effectors

The genus Salmonella contains the most common foodborne pathogens frequently isolated from food-producing animals and is responsible for zoonotic infections in humans and animals. Salmonella infection in humans and animals can cause intestinal damage, resulting in intestinal inflammation and disruption of intestinal homeostasis more severe cases can lead to bacteremia. Pyroptosis, a proinflammatory form of programmed cell death, is involved in many disease processes. Inflammasomes, pyroptosis, along with their respective signaling cascades, are instrumental in the preservation of intestinal homeostasis. In recent years, with the in-depth study of pyroptosis, our comprehension of the virulence factors and effector proteins in Salmonella has reached an extensive level, a deficit persists in our knowledge regarding the intrinsic pathogenic mechanisms about pyroptosis, necessitating a continued pursuit of understanding and investigation. In this review, we discuss the occurrence of pyroptosis induced by Salmonella effectors to provide new ideas for elucidating the regulatory mechanisms through which Salmonella virulence factors and effector proteins trigger pyroptosis could pave the way for novel concepts and strategies in the clinical prevention of Salmonella infections and the treatment of associated diseases.

Dominant immune tolerance in the intestinal tract imposed by RelB-dependent migratory dendritic cells regulates protective type 2 immunity

Dendritic cells (DCs) are crucial for initiating protective immune responses and have also been implicated in the generation and regulation of Foxp3+ regulatory T cells (Treg cells). Here, we show that in the lamina propria of the small intestine, the alternative NF-κB family member RelB is necessary for the differentiation of cryptopatch and isolated lymphoid follicle-associated DCs (CIA-DCs). Moreover, single-cell RNA sequencing reveals a RelB-dependent signature in migratory DCs in mesenteric lymph nodes favoring DC-Treg cell interaction including elevated expression and release of the chemokine CCL22 from RelB-deficient conventional DCs (cDCs). In line with the key role of CCL22 to facilitate DC-Treg cell interaction, RelB-deficient DCs have a selective advantage to interact with Treg cells in an antigen-specific manner. In addition, DC-specific RelB knockout animals show increased total Foxp3+ Treg cell numbers irrespective of inflammatory status. Consequently, DC-specific RelB knockout animals fail to mount protective Th2-dominated immune responses in the intestine after infection with Heligmosomoides polygyrus bakeri. Thus, RelB expression in cDCs acts as a rheostat to establish a tolerogenic set point that is maintained even during strong type 2 immune conditions and thereby is a key regulator of intestinal homeostasis.

The expression of intestinal Cyp2c55 is regulated by the microbiota and inflammation.

Although the mutualistic relationship between the intestinal microbiota and the human host is crucial for maintaining health, the underlying mechanisms of this relationship remain unclear. In the present study, aiming to elucidate the regulatory mechanisms governing the Cyp2c55 expression, which is predominantly observed in colonic tissues, germ-free, antibiotic-administered and colitic mice, as well as mouse colonoids, were used as experimental models. RNA sequencing showed comparable decreases in the colonic Cyp2c55 expression in germ-free and antibiotic-administered mice, when compared with that in specific pathogen-free mice. Furthermore, administration of dextran sulfate sodium decreased the Cyp2c55 expression in colitic mice. For these mice, a Pearson correlation analysis also showed a positive correlation between the Cyp2c55 expression and unconjugated bile acids (BAs), including chenodeoxycholic, muricholic, deoxycholic, lithocholic, and ursodeoxycholic acids, as well as taurine (T)-conjugated secondary BAs, including deoxycholic acid. Moreover, bacterial genera, such as Muribaculaceae and unclassified Lachnospiraceae, also exhibited a positive correlation with these BAs. While administration of an agonist of the pregnane X receptor (PXR) increased the Cyp2c55 expression in mouse colonoids, inflammatory cytokines decreased it. In conclusion, Cyp2c55 was highly expressed in the colonic epithelial cells of mice in a microbiota-dependent manner. The underlying mechanism seemed to involve a BA-mediated PXR activation. In addition, the colonic expression of Cyp2c55 was regulated by the inflammatory response. Although the physiological function of Cyp2c55 remains largely unidentified, our findings suggested that Cyp2c55 may play a role in the mutualistic interaction between the intestinal microbiota and the intestinal homeostasis.

Next-generation IgA-SEQ allows for high-throughput, anaerobic, and metagenomic assessment of IgA-coated bacteria

BackgroundThe intestinal microbiota plays a significant role in maintaining systemic and intestinal homeostasis, but can also influence diseases such as inflammatory bowel disease (IBD) and cancer. Certain bacterial species within the intestinal tract can chronically activate the immune system, leading to low-grade intestinal inflammation. As a result, plasma cells produce high levels of secretory antigen-specific immunoglobulin A (IgA), which coats the immunostimulatory bacteria. This IgA immune response against intestinal bacteria may be associated with the maintenance of homeostasis and health, as well as disease. Unraveling this dichotomy and identifying the immunostimulatory bacteria is crucial for understanding the relationship between the intestinal microbiota and the immune system, and their role in health and disease.IgA-SEQ technology has successfully identified immunostimulatory, IgA-coated bacteria from fecal material. However, the original technology is time-consuming and has limited downstream applications. In this study, we aimed to develop a next-generation, high-throughput, magnet-based sorting approach (ng-IgA-SEQ) to overcome the limitations of the original IgA-SEQ protocol.ResultsWe show, in various settings of complexity ranging from simple bacterial mixtures to human fecal samples, that our magnetic 96-well plate-based ng-IgA-SEQ protocol is highly efficient at sorting and identifying IgA-coated bacteria in a high-throughput and time efficient manner. Furthermore, we performed a comparative analysis between different IgA-SEQ protocols, highlighting that the original FACS-based IgA-SEQ approach overlooks certain nuances of IgA-coated bacteria, due to the low yield of sorted bacteria. Additionally, magnetic-based ng-IgA-SEQ allows for novel downstream applications. Firstly, as a proof-of-concept, we performed metagenomic shotgun sequencing on 10 human fecal samples to identify IgA-coated bacterial strains and associated pathways and CAZymes. Secondly, we successfully isolated and cultured IgA-coated bacteria by performing the isolation protocol under anaerobic conditions.ConclusionsOur magnetic 96-well plate-based high-throughput next-generation IgA-SEQ technology efficiently identifies a great number of IgA-coated bacteria from fecal samples. This paves the way for analyzing large cohorts as well as novel downstream applications, including shotgun metagenomic sequencing, culturomics, and various functional assays. These downstream applications are essential to unravel the role of immunostimulatory bacteria in health and disease.-iBMnzqwvJXR12FS2s7VEFVideo

Immunomodulatory Effects of a Prebiotic Formula with 2'-Fucosyllactose and Galacto- and Fructo-Oligosaccharides on Cyclophosphamide (CTX)-Induced Immunosuppressed BALB/c Mice via the Gut-Immune Axis.

Obejectives: This study explored the immunomodulatory effects of a prebiotic formula consisting of 2'-fucosyllactose (2'-FL), galacto-oligosaccharides (GOSs), and fructo-oligosaccharides (FOSs) (hereinafter referred to as 2FGF) in cyclophosphamide (CTX)-induced immunosuppressed BALB/c mice and its underlying mechanisms. Methods: Sixty healthy female BALB/c mice were randomly divided into the following groups: normal control (NC) group; CTX treatment (CTX) group; 2FGF low-dose (2FGF-L) group; 2FGF medium-dose (2FGF-M) group; and 2FGF high-dose (2FGF-H) group. An immunosuppressed model was established in the 2FGF-H group by intraperitoneal injection of 80 mg/kg CTX. After 30 days of 2FGF intervention, peripheral blood, spleen tissue, thymus tissue, and intestinal tissue from the mice were collected and analyzed. The changes in weight and food intake of the mice were recorded weekly. Hematoxylin-eosin (HE) staining was used to observe the histological change of the spleen tissue. Enzyme-linked immunosorbent assay (ELISA) was employed to detect cytokine levels in peripheral blood. Flow cytometry was used to analyze T lymphocyte subgroup ratio of splenic lymphocytes. Western blot analysis was conducted on intestinal tissues to assess the expression of proteins involved in the tight junction, toll-like receptor 4 (TLR4), mitogen-activated protein kinase (MAPK), and nuclear factor kappa-light-chain-enhancer of activated B cell (NF-κB) signaling pathways. Additionally, molecular techniques were used to analyze the intestinal microbiota. Results: The results showed that 2FGF restored CTX-induced splenic injury, increased the number of splenic T lymphocytes, and elevated serum cytokines such as interleukin-4 (IL-4) and IL-10. In the intestine, 2FGF upregulated the expression of intestinal epithelial tight junction proteins such as Claudin-1 and zonula occludens 1 (ZO-1), thereby enhancing intestinal barrier function and activating the MAPK and NF-κB pathways via TLR4. Furthermore, 2FGF elevated the α-diversity (Shannon and Simpson indices) of the gut microbiota in CTX-induced immunosuppressed mice, enriching bacteria species positively correlated with anti-inflammatory cytokines (e.g., IL-4) such as g_Streptomyces and g_Bacillus and negatively correlated with pro-inflammatory cytokines (e.g., IL-1β) such as g_Saccharomyces. The results suggest that 2FGF may enhance immunity via the gut-immune axis. Conclusions: The 2FGF prebiotic formula showed an immunomodulatory effect in CTX-induced immunosuppressed mice, and the mechanism of which might involve optimizing the gut flora, enhancing intestinal homeostasis, strengthening the intestinal barrier, and promoting the expression of immune factors by regulating the TLR-4/MAPK/NF-κB pathway.

Intestinal homeostasis disrupted by Periodontitis exacerbates Alzheimer’s Disease in APP/PS1 mice

Periodontitis exacerbates Alzheimer’s disease (AD) through multiple pathways. Both periodontitis and AD are intricately correlated to intestinal homeostasis, yet there is still a lack of direct evidence regarding whether periodontitis can regulate the progression of AD by modulating intestinal homeostasis. The current study induced experimental periodontitis in AD mice by bilaterally ligating the maxillary second molars with silk and administering Pg-LPS injections in APPswe/PS1ΔE9 (APP/PS1) mice. Behavioral tests and histological analyses of brain tissue were conducted after 8 weeks. Gut microbiota was analyzed and colon tissue were also evaluated. Then, fecal microbiota from mice with periodontitis was transplanted into antibiotic-treated mice to confirm the effects of periodontitis on AD and the potential mechanism was explored. The results indicated periodontitis exacerbated cognitive impairment and anxious behaviour in APP/PS1 mice, with increased Aβ deposition, microglial overactivation and neuroinflammation in brain. Moreover, the intestinal homeostasis of AD mice was altered by periodontitis, including affecting gut microbiota composition, causing colon inflammation and destroyed intestinal epithelial barrier. Furthermore, AD mice that underwent fecal transplantation from mice with periodontitis exhibited worsened AD progression and disrupted intestinal homeostasis. It also impaired intestinal barrier function, elevated peripheral inflammation, damaged blood-brain barrier (BBB) and caused neuroinflammation and synapses impairment. Taken together, the current study demonstrated that periodontitis could disrupt intestinal homeostasis to exacerbate AD progression potential via causing gut microbial dysbiosis, intestinal inflammation and intestinal barrier impairment to induce peripheral inflammation and damage BBB, ultimately leading to neuroinflammation and synapse impairment. It underscores the importance of maintaining both periodontal health and intestinal homeostasis to reduce the risk of AD.

The Intestinal Transporter SLC30A1 Plays a Critical Role in Regulating Systemic Zinc Homeostasis.

The essential trace element, zinc, regulates virtually all aspects of cellular physiology, particularly cell proliferation and survival. Diverse families of metal transporters, metallothioneins, and metal-responsive transcriptional regulators are linked to zinc homeostasis. However, the mechanism underlying the regulation of systemic zinc homeostasis remains largely unknown. Here, it is reported that the intestinal transporter SLC30A1 plays an essential role in maintaining systemic zinc homeostasis. Using several lines of tissue-specific knockout mice, it is found that intestinal Slc30a1 plays a critical role in survival. Furthermore, lineage tracing reveals that Slc30a1 is localized to the basolateral membrane of intestinal epithelial cells (IECs). It is also found that Slc30a1 safeguards both intestinal barrier integrity and systemic zinc homeostasis. Finally, an integrative analysis of the cryo-EM structure and site-specific mutagenesis of human SLC30A1 are performed and a zinc transport mechanism of SLC30A1 unique within the SLC30A family, with His43 serving as a critical residue for zinc selectivity, is identified.

Neuro-immune cell interactions in the regulation of intestinal immune homeostasis.

Bidirectional regulation between neurons and immune cells in the intestine governs essential physiological processes, including digestion, metabolism and motility, while also controlling intestinal inflammation and maintaining tissue homeostasis. This review covers recent advances and future research challenges focused on the regulatory molecules and potential therapeutic targets in neuron-immune interactions within the intestine. Recently identified molecular and cellular pathways have been shown to regulate neuron-immune cell cross talk in the context of maintaining tissue homeostasis, modulating inflammation, and promoting intestinal repair. Additionally, behaviors governed by the central nervous system, including feeding and stress responses, can play key roles in regulating intestinal immunity and inflammation. This review emphasizes recent progress in understanding the complex interplay between the nervous system and intestinal immune system and outlines future research directions. These advances have the potential to lead to innovative therapies targeting gastrointestinal disorders including inflammatory bowel diseases, allergic responses and cancer.

Apoptotic and proliferative processes in the small intestine of rats with type 2 diabetes mellitus after metformin and propionic acid treatment

BackgroundPropionic acid (PA) is an intermediate product of metabolism of intestinal bacteria and may protect the intestinal barrier from disruption. The aim of the study was to investigate the apoptotic and proliferative processes in the small intestine (SI) of rats with type 2 diabetes mellitus (T2DM) on the background of metformin monotherapy and its combination with PA.MethodsMale Wistar rats were divided: 1) control; 2) T2DM (3-month high-fat diet followed by streptozotocin injection of 25 mg/kg of body weight); 3) T2DM + metformin (60 mg/kg, 14 days, orally); 4) T2DM + PA (60 mg/kg, 14 days, orally); 5) T2DM + PA + metformin. Western blotting, RT-PCR, and scanning electron microscopy were performed.ResultsWe observed profound changes in the SI of diabetic rats suggesting the disturbed intestinal homeostasis: impaired mitochondrial ultrastructure, increased cristae volume, and decreased content of proliferative marker Ki67 with almost unchanged proapoptotic caspase-3 and its p17 subunit levels. Metformin and PA monotherapies also led to an increased cristae volume, however, after their combination, a tendency to normalization of ultrastructure of mitochondria was observed. While there was a significant inhibition of proliferation in T2DM and, in greater extent, after metformin and PA monotherapies, differential influence on apoptosis in the SI was observed. While metformin inhibited apoptosis via Bax declining, PA mainly acted via caspase-3-dependent mechanism elevating its active p17 subunit.ConclusionPA supplementation for the improvement of diabetes-induced gastrointestinal complications concurrently with metformin may be consider as a perspective supportive therapy. Data related to PA action on SI may be valuable during the development of new treatment strategies for diabetes-induced intestinal disturbances raised after metformin treatment.

Evaluating the Effectiveness of Probiotic Supplementation in Combination With Doxycycline for the Treatment of Moderate Acne: A Randomized Double-Blind Controlled Clinical Trial.

Acne is a chronic inflammatory skin disease that negatively affects patients' quality of life. Increasing antibiotic resistance is making acne less responsive to treatment. Probiotics are live microorganisms that can provide health benefits by fighting pathogens and maintaining intestinal homeostasis and skin microbiome balance. This study investigates the effects of probiotics in the treatment of acne vulgaris. In this randomized controlled clinical trial, 80 patients with moderate acne were divided into two groups of 40. All patients received the same topical treatment, which consisted of a daily antibacterial face wash and Adapalene gel every other night. The control group received one capsule of doxycycline (100 mg) daily, whereas the intervention group received one probiotic capsule daily in addition to doxycycline. Patients underwent photography of facial acne lesions, and treatment response was assessed using the global acne grading system (GAGS) and acne grading method at baseline, as well as during follow-up visits at 1, 2, and 3 months. The global acne grading system indicated that both groups showed improvement. However, analyses revealed that outcomes were significantly better in the doxycycline plus probiotics group for the forehead (p = 0.018), chin (p = 0.021), and nose (p = 0.021). No significant differences were observed for the left and right cheeks, back, and chest areas, with the mean GAGS score reduction between the two groups differing by only 2%. Treatment with probiotics significantly reduced the severity of lesions compared to the control group (p < 0.001). The acne grading method also indicated that the intervention group had a significantly better treatment response than the control group (p < 0.001). Furthermore, treatment with probiotics did not result in any side effects. Probiotics can serve as an effective and safe treatment option, enhancing the outcomes of routine acne treatments, particularly for patients with acne on the forehead, chin, and nose.

Kui-Jie-Ling capsule inhibits ulcerative colitis by modulating inflammation and gut microbiota.

Kui-Jie-Ling capsule (Kui-Jie-Ling) is a hospital preparation for ulcerative colitis (UC) in China. This study aimed at evaluating the protective effects and mechanisms of Kui-Jie-Ling and Kui-Jie-Ling combined with adalimumab on UC induced by dextran sulfate sodium (DSS). Network pharmacology was combined with an animal experiment to reveal the targets of Kui-Jie-Ling alleviating UC. The UC model was established by drinking 2.5% DSS solution for 7days. On the second day, the mice in the Kui-Jie-Ling group were orally administered with Kui-Jie-Ling (1.5 and 3.0g/kg) daily for seven consecutive days, and the mice in the combination group were orally administered with Kui-Jie-Ling (3.0g/kg) once a day for seven consecutive days and received one subcutaneous injection of adalimumab. The disease activity index, the colon length, the spleen index, the cytokines, the colon, the short-chain fatty acid content, and the gut microbiota in the colon were analyzed. The role of gut microbiota against UC was verified by fecal microbiota transplantation experiments. The animal study's results were consistent with the network pharmacology analysis, which reflected that Kui-Jie-Ling alleviated UC via multi-pathway. Kui-Jie-Ling ameliorated UC by inhibiting the formation of neutrophil extracellular traps (NETs), regulating inflammatory factors through the lipopolysaccharide-toll-like receptor 4/nuclear factor kappa B and interleukin-23-Janus kinase 2/signal transducer and activator of transcription 3 signaling pathway, and restoring intestinal homeostasis. These studies provided the experimental basis for the clinical administration of Kui-Jie-Ling and Kui-Jie-Ling combined with adalimumab against UC.

Clostridium sporogenes-derived metabolites protect mice against colonic inflammation

ABSTRACT Gut microbiota-derived metabolites play a pivotal role in the maintenance of intestinal immune homeostasis. Here, we demonstrate that the human commensal Clostridium sporogenes possesses a specific metabolic fingerprint, consisting predominantly of the tryptophan catabolite indole-3-propionic acid (IPA), the branched-chain acids (BCFAs) isobutyrate and isovalerate and the short-chain fatty acids (SCFAs) acetate and propionate. Mono-colonization of germ-free mice with C. sporogenes (CS mice) affected colonic mucosal immune cell phenotypes, including up-regulation of Il22 gene expression, and increased abundance of transcriptionally active colonic tuft cells and Foxp3+ regulatory T cells (Tregs). In DSS-induced colitis, conventional mice suffered severe inflammation accompanied by loss of colonic crypts. These symptoms were absent in CS mice. In conventional, but not CS mice, bulk RNAseq analysis of the colon revealed an increase in inflammatory and Th17-related gene signatures. C. sporogenes-derived IPA reduced IL-17A protein expression by suppressing mTOR activity and by altering ribosome-related pathways in Th17 cells. Additionally, BCFAs and SCFAs generated by C. sporogenes enhanced the activity of Tregs and increased the production of IL-22, which led to protection from colitis. Collectively, we identified C. sporogenes as a therapeutically relevant probiotic bacterium that might be employed in patients with inflammatory bowel disease (IBD).