Inflammatory bowel disease (IBD) is a chronic disorder characterized by recurrent gastrointestinal inflammation, lacking a precise aetiology and definitive cure. The gut microbiome is vital in preventing and treating IBD due to its various physiological functions. In the interplay between the gut microbiome and human health, extracellular vesicles secreted by gut bacteria (BEVs) are key mediators. Herein, we explore the role of Roseburia intestinalis (R)‐derived EVs (R‐EVs) as potent anti‐inflammatory mediators in treating dextran sulfate sodium‐induced colitis. R was selected as an optimal BEV producer for IBD treatment through ANCOM analysis. R‐EVs with a 76 nm diameter were isolated from R using a tangential flow filtration system. Orally administered R‐EVs effectively accumulated in inflamed colonic tissues and increased the abundance of Bifidobacterium on microbial changes, inhibiting colonic inflammation and prompting intestinal recovery. Due to the presence of Ile‐Pro‐Ile in the vesicular structure, R‐EVs reduced the DPP4 activity in inflamed colonic tissue and increased the active GLP‐1, thereby downregulating the NFκB and STAT3 via the PI3K pathway. Our results shed light on the impact of BEVs on intestinal recovery and gut microbiome alteration in treating IBD.

Leaky gut symptoms and inflammatory bowel disease (IBD) are associated with damaged intestinal mucosa, intestinal permeability dysfunction by epithelial cell cytoskeleton contraction, disrupted intercellular tight junction (TJ) protein expression, and abnormal immune responses and are intractable diseases. We evaluated the effects of schisandrin C, a dibenzocyclooctadiene lignan from Schisandra chinensis, on intestinal inflammation and permeability dysfunction in gut mimetic systems: cultured intestinal cells, intestinal organoids, and a Caenorhabditis elegans model. Schisandrin C was selected from 9 lignan compounds from S. chinensis based on its anti-inflammatory effects in HT-29 human intestinal cells. IL-1β and Pseudomonas aeruginosa supernatants were used to disrupt intestinal barrier formation in vitro and in C. elegans, respectively. The effects of schisandrin C on transepithelial electrical resistance (TEER) and intestinal permeability were evaluated in intestinal cell monolayers, and its effect on intestinal permeability dysfunction was tested in mouse intestinal organoids and C. elegans by measuring fluorescein isothiocyanate (FITC)-dextran efflux. The effect of schisandrin C on TJ protein expression was investigated by western blotting and fluorescence microscopy. The signaling pathway underlying these effects was also elucidated. Schisandrin C ameliorated intestinal permeability dysfunction in three IBD model systems and enhanced epithelial barrier formation via upregulation of ZO-1 and occludin in intestinal cell monolayers and intestinal organoids. In Caco-2 cells, schisandrin C restored IL-1β-mediated increases in MLCK and p-MLC expression, in turn blocking cytoskeletal contraction and subsequent intestinal permeabilization. Schisandrin C inhibited NF-ĸB and p38 MAPK signaling, which regulates MLCK expression and structural reorganization of the TJ complex in Caco-2 cells. Schisandrin C significantly improved abnormal FITC-dextran permeabilization in both intestinal organoids and C. elegans. Schisandrin C significantly improves abnormal intestinal permeability and regulates the expression of TJ proteins, long MLCK, p-MLC, and inflammation-related proteins, which are closely related to leaky gut symptoms and IBD development. Therefore, schisandrin C is a candidate to treat leaky gut symptoms and IBDs.

An exponential rise in studies regarding the association among human gut microbial communities, human health, and diseases is currently attracting the attention of researchers to focus on human gut microbiome research. However, even with the ever-growing number of studies on the human gut microbiome, translation into improved health is progressing slowly. This hampering is due to the complexities of the human gut microbiome, which is composed of >1,000 species of microorganisms, such as bacteria, archaea, viruses, and fungi. To overcome this complexity, it is necessary to reduce the gut microbiome, which can help simplify experimental variables to an extent, such that they can be deliberately manipulated and controlled. Reconstruction of synthetic or established gut microbial communities would make it easier to understand the structure, stability, and functional activities of the complex microbial community of the human gut. Here, we provide an overview of the developments and challenges of the synthetic human gut microbiome, and propose the incorporation of multi-omics and mathematical methods in a better synthetic gut ecosystem design, for easy translation of microbiome information to therapies.

Probiotics, live microorganisms that confer health benefits when consumed in adequate amounts, have gained significant attention for their potential therapeutic applications. The beneficial effects of probiotics are believed to stem from their ability to enhance intestinal barrier function, inhibit pathogens, increase beneficial gut microbes, and modulate immune responses. However, clinical studies investigating the effectiveness of probiotics have yielded conflicting results, potentially due to the wide variety of probiotic species and strains used, the challenges in controlling the desired number of live microorganisms, and the complex interactions between bioactive substances within probiotics. Bacterial cell wall components, known as effector molecules, play a crucial role in mediating the interaction between probiotics and host receptors, leading to the activation of signaling pathways that contribute to the health-promoting effects. Previous reviews have extensively covered different probiotic effector molecules, highlighting their impact on immune homeostasis. Understanding how each probiotic component modulates immune activity at the molecular level may enable the prediction of immunological outcomes in future clinical studies. In this review, we present a comprehensive overview of the structural and immunological features of probiotic effector molecules, focusing primarily on Lactobacillus and Bifidobacterium. We also discuss current gaps and limitations in the field and propose directions for future research to enhance our understanding of probiotic-mediated immunomodulation.

Chlorella vulgaris (C. vulgaris) is unicellular green algae consumed worldwide as a functional food. The immune stimulatory function of C. vulgaris is known; however, no study has elucidated its immune regulatory potential and associated microbiome modulation. In the current study, we aimed to validate the immune regulatory role of C. vulgaris mediated through two mechanisms. Initially, we assessed its ability to promote the expansion of the regulatory T cell (Treg) population. Subsequently, we investigated its impact on gut microbiota composition and associated metabolites. The supplementation of C. vulgaris altered the gut microbiota composition, accompanied by increased short-chain fatty acid (SCFAs) production in mice at homeostasis. We later used C. vulgaris in the treatment of a DSS-induced colitis model. C. vulgaris intervention alleviated the pathological symptom of colitis in mice, with a corresponding increase in Treg levels. As C. vulgaris is a safe and widely used food supplement, it can be a feasible strategy to instigate cross-talk between the host immune system and the intestinal flora for the effective management of inflammatory bowel disease (IBD).