Viral diseases remain a significant global challenge. Although vaccination is the primary strategy for preventing viral infections, the rapid evolution of viruses and their divergence from existing vaccines limit vaccine efficacy. Therefore, novel and safe alternatives to combat viral infections are urgently needed. Probiotic-derived extracellular vesicles (PEVs), lipid bilayer-enclosed nanoparticles, exhibit potential as safe alternatives to live bacteria for treating viral diseases. These vesicles deliver antiviral molecules through mechanisms such as blocking viral adsorption/invasion and modulating host immune responses. This review systematically summarizes the biological characteristics of PEVs, their antiviral mechanisms, and their potential applications against respiratory, enteric, and enveloped viruses. Additionally, recent advances in engineering strategies, clinical translation challenges, and future directions for PEVs are discussed.

Obesity and type 2 diabetes (T2D) are two of the most common health problems in the world, particularly in adult Asians, with a significant impact on morbidity and mortality. Numerous studies have revealed that the gut microbiome of people with obesity and T2D differs significantly from those of healthy people. Those who suffer from certain illnesses often encounter disruption in their gut microbiome, leading to a decrease in richness diversity and diminished microbial activity. This disruption can also result in the loss of the gut mucosal barrier, increased gut permeability, and most likely, the development of a leaky gut. Recent studies have also emphasized the essential role of the gut microbiome in these conditions. However, conflicting findings were found between one study and another investigation. Therefore, this paper aims to provide an overview of gut microbiome characteristics in adult Asians with obesity, T2D, and the combination of both. In addition, this paper elaborates on the current understanding regarding the association of the gut microbiome with health status, thereby serving as a foundation for developing probiotics or prebiotics to modulate the gut microbiome and improve metabolic health.

Secretory IgA (sIgA) is a class of antibodies that plays a pivotal role in mucosal immunity. The sIgA secreted into the intestinal tract acts to prevent luminal pathogens and food antigens from penetrating across the intestinal epithelial barrier, thereby contributing to the suppression of infections and food allergies. Furthermore, it binds extensively to symbiotic bacteria, exerting a significant impact on the gut microbiota. The antigen recognition specificity of antibodies is determined by the amino acid sequence of the variable region. Therefore, the type of IgA repertoire influences the formation and maintenance of the gut microbiota and susceptibility to infection and food allergy. The initial repertoire of IgA is induced by the extensive colonization of intestinal bacteria during the weaning period and is maintained for an extended period. However, the relationship between the initial gut microbiota and IgA repertoire development has yet to be fully analyzed. In the present study, the weaning gut microbiota was disrupted with antibiotics, and the IgA repertoire was subsequently analyzed in young adulthood. The administration of antibiotics during the weaning period resulted in the suppression of somatic hypermutation in the variable regions of IgA expressed in the small intestine, as well as an impact on multivalent reactivity in IgA during early childhood. Additionally, disturbances in the weaning gut microbiota led to alterations in the microbiota structure of adolescent mice. These findings suggest that the weaning gut microbiota plays a role in promoting the maturation of IgA function.

Dysbiosis of the gut microbiota has recently been identified as a therapeutic target for ulcerative colitis. We reported the effectiveness of antibiotic combination therapy (ATM therapy) for the induction and maintenance of ulcerative colitis remission. In this study, we aimed to investigate the long-term effectiveness of ATM therapy in a larger cohort. A prospective open-label trial was undertaken with 311 adult ulcerative colitis patients. The combination of oral amoxicillin 500 mg t.i.d., tetracycline 500 mg t.i.d. and metronidazole 250 mg t.i.d. was administered to patients daily for 2–4 weeks in addition to their conventional medication. Clinical assessments were performed using the partial Mayo score at baseline; at treatment completion; and at 3, 6, 9 and 12 months. Endoscopic evaluations were performed using the Mayo endoscopic score at baseline, 3 months, and 12 months. The compliance rate was 95.7%. The response and remission rates were 75.2% and 30.9% at completion, 62.7% and 29.6% at 3 months, 48.2% and 27.7% at 6 months, 37.9% and 24.4% at 9 months, and 35.4% and 24.4% at 12 months. The most frequent adverse events were diarrhea and fever. No life-threatening adverse events were observed during the trial. ATM therapy effectively led to long-term clinical response and remission in patients with active ulcerative colitis symptoms. However, further investigations are needed for the standardization of antibiotic therapy for ulcerative colitis in the future.

Based on liver FibroTouch technology combined with 16S rRNA gene sequencing technology, this study aimed to explore the changes of liver fibrosis indexes and intestinal flora in Wilson’s disease (WD) improved by Gandouling (GDL). Ninety patients with WD hepatic fibrosis at the Brain Disease Center of the Anhui Provincial Hospital of Traditional Chinese Medicine were included and randomly divided into an observation group and a control group for a 48-day randomized, double-blind, placebo-controlled trial. Patients in both groups were treated with conventional sodium dimercaptopropanesulfonate, to which GDL was added in the observation group, while the control group was given the corresponding placebo treatment. Before and after treatment, liver stiffness was assessed, blood samples were collected for laboratory tests, and stool samples were collected for 16S rRNA sequencing. Supplementation with GDL significantly improved liver stiffness and non-invasive liver fibrosis modeling indicators, while alanine aminotransferase, aspartate aminotransferase, gamma-glutamyltransferase, bile acid, platelets, hyaluronic acid and laminin levels were also significantly improved (p<0.05). Other parameters showed no significant changes. The results of intestinal microbial testing showed that the microbial diversity and composition of the patients in the observation group underwent significant optimization, in which the number of probiotics rose but the number of pathogenic and opportunistic pathogens declined and even basically returned to the normal range. GDL combined with conventional liver-protecting and copper-removing treatments can effectively improve patients’ liver fibrosis-related indexes. Furthermore, GDL has the ability to regulate the composition and diversity of the intestinal flora and promote reconstruction of the intestinal microbial community, which in turn may reverse the state of hepatic fibrosis.

Non-alcoholic fatty liver disease (NAFLD) is a prevalent liver disorder characterized by hepatic fat accumulation unrelated to alcohol consumption, with its prevalence rising alongside obesity rates. The gut-liver axis reveals that gut microbiota and metabolites significantly impact NAFLD development and progression. This study aimed to investigate the effects of probiotic Lactiplantibacillus plantarum Dad-13 on body weight, liver function, and histopathological features in a rat model of NAFLD. The experimental protocol involved administering probiotic L. plantarum Dad-13 at a dose of 3 × 10⁹ CFU/g over six weeks to rats with NAFLD induced by a high-fat and high-fructose (HFFr) diet. The results demonstrated significant reductions in body and liver weight, improved liver function (serum lipopolysaccharide binding protein, aspartate aminotransferase, and alanine aminotransferase levels), and improved the non-alcoholic liver activity score in rats fed HFFr diets supplemented with probiotics. These findings suggest that supplementation with probiotic L. plantarum Dad-13 is a promising therapeutic intervention for NAFLD.

Our previous study showed that the intragastric administration of Lactiplantibacillus plantarum No. 14 reduces adipocyte size in white adipose tissue of high-fat diet (HFD)-induced obese mice. We also suggested that the anti-inflammatory effect of L. plantarum No. 14 in white adipose tissues is mediated, at least in part, by circulating exosomes, a type of extracellular vesicle (EV). Therefore, the present study examined whether EVs mediate the adipocyte size-reducing effect of L. plantarum No. 14. Macrophages derived from mouse bone marrow were co-cultured with L. plantarum No. 14, and EVs were isolated from the culture supernatant by ultracentrifugation. C57BL/6J mice fed an HFD were intravenously administered the EVs 5 times a week for 7 weeks. We found that the average adipocyte size was significantly lower in mice administered EVs isolated from the culture supernatant of macrophages co-cultured with L. plantarum No. 14 than in those administered EVs isolated from the culture supernatant of macrophages without co-culture and those administered PBS. In adipocytically differeintiating 3T3-L1 cells, supplementation of EVs isolated from the culture supernatant of macrophages co-cultured with L. plantarum No. 14 reduced adipogenesis, as evidenced by AdipoRed staining. Furthermore, the mRNA levels of adipogenesis-related genes and insulin-induced glucose uptake were also reduced by supplementation with EVs isolated from the culture supernatant of macrophages co-cultured with L. plantarum No. 14. These results suggest that circulating EVs shed by macrophages are involved in the adipocyte size-reducing effect of L. plantarum No. 14 by reducing adipogenesis-related gene expression and glucose uptake in adipocytes.

Heated eggs have often been used for oral immunotherapy of egg allergy because of their lower allergenicity than raw eggs. Furthermore, recent guidelines recommend the earlier introduction of well-cooked eggs to the diet as a supplementary food and protective measure against food allergy in infants. However, the influence of cooking with heat on the allergenicity and tolerogenicity of egg white (EW) antigen in individuals with egg allergy is not well understood. We investigated this by feeding ovalbumin (OVA)-sensitized inbred mice EW heated at 80°C for 15 min (80EW), 100°C for 5 min (100EW), or 121°C for 40 min (121EW). Only 100EW resolved enteritis, and it produced more effective tolerogenicity to OVA than EW. The state of enteritis and tolerogenicity for 80EW was almost the same as that for EW. Th1 responses to short-term feeding were observed with 121EW. We then investigated allergy recurrence after continuous feeding with the 100EW diet. Of note, however, the oral tolerance acquired with 100EW or EW was not effective against allergic recurrence in response to EW, because of residual high levels of serum OVA-specific IgE and residual infiltrated mast cells in the intestine. Furthermore, the recurrence of allergic symptoms in response to EW was more severe when oral tolerance was acquired with 100EW rather than with EW. Our results suggest that patients must be careful not to inadvertently consume EW, even if clinical tolerance to heat-treated EW has been achieved.

Barley β-glucan (BGL), a dietary fiber composed of β1,3- and β1,4-linked glucose units, confers various health benefits, including anti-diabetic effects. A previous study reported that the anti-diabetic effect of BGL was associated with gut bacteria, particularly Segatella copri. Recently, a study using recombinant proteins revealed the biochemical characteristics of proteins encoded by the polysaccharide utilization locus 4 (PUL4), which is implicated in BGL assimilation. However, the precise physiological roles of PUL4 remain unclear. In this study, we used gene disruption in S. copri JCM 13464^T (=DSM 18205^T; also known as Prevotella copri CB7) to investigate the physiological functions of PUL4 under BGL-supplemented conditions. Deletion of pul4 significantly reduced bacterial growth, as well as acetic and succinic acid production, indicating that PUL4 is essential for efficient BGL assimilation and key metabolite generation. Moreover, although PUL4 contributed to BGL and lichenan utilization, cello-oligosaccharide assimilation did not require PUL4, indicating the presence of additional metabolic systems in S. copri JCM 13464^T. Strain comparisons showed that one of the four S. copri strains assimilated BGL despite lacking PUL4, implying that some strains may possess alternative BGL-degrading loci other than PUL4. These findings provide direct evidence that PUL4 is an indispensable gene cluster for BGL assimilation by S. copri JCM 13464^T. Because PUL4 enhances the biomass yield on BGL, it likewise boosts total acetate and succinate formation, potentially generating health benefits.