There are limited studies on the improvement of leaky gut with minor inflammation associated with various diseases. To explore the therapeutic potential of Lactiplantibacillus plantarum 22 A-3, a member of the Lactobacillus species, in addressing a leaky gut. Lactiplantibacillus plantarum 22 A-3 was administered to a leaky gut mice model with low dextran sulfate sodium concentrations. The Lactiplantibacillus plantarum 22 A-3-treated group exhibited amelioration of increased intestinal permeability, as indicated by lower blood fluorescein isothiocyanate-dextran levels compared with that of the control group. Furthermore, the messenger RNA expression of interleukin-10, an anti-inflammatory cytokine, was upregulated in the small intestine of Lactiplantibacillus plantarum 22 A-3-treated mice. Moreover, forkhead box P3 was upregulated in the small intestine and colon following Lactiplantibacillus plantarum 22 A-3 administration. Flow cytometry showed that forkhead box P3-positive regulatory T cells tended to increase in the small intestine and colon; however, this was not significant. Messenger RNA levels for the pro-inflammatory cytokines, interleukin-1 beta, and tumor necrosis factor-alpha showed no significant changes in the small intestine; however, their expressions significantly decreased in the colon. Blood fluorescein isothiocyanate-dextran levels showed that intestinal permeability also decreased in Lactiplantibacillus plantarum 22 A-3-dead bacteria. The bacterial component of Lactiplantibacillus plantarum 22 A-3 ameliorates increased intestinal permeability through its anti-inflammatory effect in the intestinal tract and may be a novel treatment for leaky gut.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) marked by persistent inflammation of the mucosal lining of the large intestine, leading to debilitating symptoms and reduced quality of life. Emerging evidence suggests that an imbalance of the gut microbiota plays a crucial role in UC pathogenesis, and various signaling pathways are implicated in the dysregulated immune response. Probiotics are live microorganisms that confer health benefits to the host, have attracted significant attention for their potential to restore gut microbial balance and ameliorate inflammation in UC. Recent studies have elucidated the mechanisms by which probiotics modulate these signaling pathways, often by producing anti-inflammatory molecules and promoting regulatory immune cell function. For example, probiotics can inhibit the nuclear factor-κB (NF-κB) pathway by stabilizing Inhibitor of kappa B alpha (IκBα), dampening the production of proinflammatory cytokines. Similarly, probiotics can modulate the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway, suppressing the activation of STAT1 and STAT3 and thus reducing the inflammatory response. A better understanding of the underlying mechanisms of probiotics in modulating pathogenic signaling pathways in UC will pave the way for developing more effective probiotic-based therapies. In this review, we explore the mechanistic role of probiotics in the attenuation of pathogenic signaling pathways, including NF-κB, JAK/STAT, mitogen-activated protein kinases (MAPKs), Wnt/β-catenin, the nucleotide-binding domain (NOD)-, leucine-rich repeat (LRR)- and pyrin domain-containing protein 3 (NLRP3) inflammasome, Toll-like receptors (TLRs), interleukin-23 (IL-23)/IL-17 signaling pathway in UC.

Traditional Chinese medicine has used the drug Pien Tze Huang (PTH), a classic prescription, to treat autoimmune hepatitis (AIH). However, the precise mode of action is still unknown.

To investigate the mechanism of PTH in an AIH mouse model by determining the changes in gut microbiota structure and memory regulatory T (mTreg) cells functional levels.

Following induction of the AIH mouse model induced by Concanavalin A (Con A), prophylactic administration of PTH was given for 10 d. The levels of mTreg cells were measured by flow cytometry, and intestinal microbiota was analyzed by 16S rRNA analysis, while western blotting was used to identify activation of the toll-like receptor (TLR)2, TLR4/nuclear factor-κB (NF-κB), and CXCL16/CXCR6 signaling pathways.

In the liver of mice with AIH, PTH relieved the pathological damage and reduced the numbers of T helper type 17 cells and interferon-γ, tumor necrosis factor-alpha, interleukin (IL)-1β, IL-2, IL-6, and IL-21 expression. Simultaneously, PTH stimulated the abundance of helpful bacteria, promoted activation of the TLR2 signal, which may enhance Treg/mTreg cells quantity to produce IL-10, and suppressed activation of the TLR4/NF-κB and CXCL16/CXCR6 signaling pathways.

PTH regulates intestinal microbiota balance and restores mTreg cells to alleviate experimental AIH, which is closely related to the TLR/CXCL16/CXCR6/NF-κB signaling pathway.

Ulcerative colitis (UC) is a persistent inflammatory disorder that affects the gastrointestinal tract, mainly the colon, which is defined by inflammatory responses and the formation of ulcers. Probiotics have been shown to directly impact various immune cells, including dendritic cells (DCs), macrophages, natural killer (NK) cells, and T and B cells. By interacting with cell surface receptors, they regulate immune cell activity, produce metabolites that influence immune responses, and control the release of cytokines and chemokines.

This article is a comprehensive review wherein we conducted an exhaustive search across published literature, utilizing reputable databases like PubMed and Web of Science. Our focus centered on pertinent keywords, such as "UC," 'DSS," "TNBS," "immune cells," and "inflammatory cytokines," to compile the most current insights regarding the therapeutic potential of probiotics in managing UC.

This overview aims to provide readers with a comprehensive understanding of the effects of probiotics on immune cells in relation to UC. Probiotics have a crucial role in promoting the proliferation of regulatory T cells (Tregs), which are necessary for preserving immunological homeostasis and regulating inflammatory responses. They also decrease the activation of pro-inflammatory cells like T helper 1 (Th1) and Th17 cells, contributing to UC development. Thus, probiotics significantly impact both direct and indirect pathways of immune cell regulation in UC, promoting Treg differentiation, inhibiting pro-inflammatory cell activation, and regulating cytokine and chemokine release.

Probiotics demonstrate significant potential in modulating the immune reactions in UC. Their capacity to modulate different immune cells and inflammation-related processes makes them a promising therapeutic approach for managing UC. However, further studies are warranted to optimize their use and fully elucidate the molecular mechanisms underlying their beneficial effects in UC treatment.

The old age-related loss of immune tolerance inflicts a person with a wide range of autoimmune and inflammatory diseases. Dendritic cells (DCs) are the sentinels of the immune system that maintain immune tolerance through cytokines and regulatory T-cells generation. Aging disturbs the microbial composition of the gut, causing immune system dysregulation. However, the vis-à-vis role of gut dysbiosis on DCs tolerance remains highly elusive. Consequently, we studied the influence of aging on gut dysbiosis and its impact on the loss of DC tolerance. We show that DCs generated from either the aged (DC^Old ) or gut-dysbiotic young (DC^Dysbiotic ) but not young (DC^Young ) mice exhibited loss of tolerance, as evidenced by their failure to optimally induce the generation of Tregs and control the overactivation of CD4⁺ T cells. The mechanism deciphered for the loss of DC^Old and DC^Dysbiotic tolerance was chiefly through the overactivation of NF-κB, impaired frequency of Tregs, upregulation in the level of pro-inflammatory molecules (IL-6, IL-1β, TNF-α, IL-12, IFN-γ), and decline in the anti-inflammatory moieties (IL-10, TGF-β, IL-4, IDO, arginase, NO, IRF-4, IRF-8, PDL1, BTLA4, ALDH2). Importantly, a significant decline in the frequency of the Lactobacillus genus was noticed in the gut. Replenishing the gut of old mice with the Lactobacillus plantarum reinvigorated the tolerogenic function of DCs through the rewiring of inflammatory and metabolic pathways. Thus, for the first time, we demonstrate the impact of age-related gut dysbiosis on the loss of DC tolerance. This finding may open avenues for therapeutic intervention for treating age-associated disorders with the Lactobacillus plantarum.

Bacterial overgrowth is common for improperly stored urine. However, its effects on human urinary extracellular vesicles (uEVs) study had not been previously examined nor documented. This study investigated the presence of bacterial EVs (bEVs) contaminated in uEVs samples and their effects on uEVs study. Nanoscale uEVs were isolated from normal human urine immediately after collection (0-h) or after 25°C-storage with/without preservative (10 mM NaN3) for up to 24-h. Turbidity, bacterial count and total uEVs proteins abnormally increased in the 8-h and 24-h-stored urine without NaN3. NanoLC-ESI-LTQ-Orbitrap MS/MS identified 6-13 bacterial proteins in these contaminated uEVs samples. PCR also detected bacterial DNAs in these contaminated uEVs samples. Besides, uEVs derived from 8-h and 24-h urine without NaN3 induced macrophage activation (CD11b and phagocytosis) and secretion of cytokines (IFN-α, IL-8, and TGF-β) from macrophages and renal cells (HEK-293, HK-2, and MDCK). All of these effects induced by bacterial contamination were partially/completely prevented by NaN3. Interestingly, macrophage activation and cytokine secretion were also induced by bEVs purified from Escherichia coli. This study clearly shows evidence of bEVs contamination and their effects on human uEVs study when the urine samples were inappropriately stored, whereas NaN3 can partially/completely prevent such effects from the contaminated bEVs.

Ulcerative colitis (UC) is a chronic nonspecific inflammatory disease with a complex etiology. Intestinal mucosal injury is an important pathological change in individuals with UC. Leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5+) intestinal stem cells (ISCs) exhibit self-renewal and high differentiation potential and play important roles in the repair of intestinal mucosal injury. Moreover, LGR5+ ISCs are intricately regulated by both the Wnt/β-catenin and Notch signaling pathways, which jointly maintain the function of LGR5+ ISCs. Combination therapy targeting multiple signaling pathways and transplantation of LGR5+ ISCs may lead to the development of new clinical therapies for UC.