Bioscience of microbiota, food and health最新文献

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.

High-fat diet (HFD)-induced alterations in gut microbiota may be associated with host pathophysiology, prompting increased interest in elucidating their causal relationships. However, the mechanisms by which HFDs induce these alterations require further clarification. Our previous study using cholic acid (CA)-fed rats suggested that bile acid drives the HFD-induced microbiota alterations as a host factor, a concept termed the "bile acid hypothesis". We analyzed the alterations in the cecal microbiota and bile acid composition in HFD-fed rats and compared the results with those of rats on a CA-supplemented diet. In both cases, the concentrations of total bile acids, including highly bactericidal deoxycholic acid (DCA), increased, concomitant with the increases in the Firmicutes (Bacillota)/Bacteroidetes (Bacteroidota) ratio. Operational taxonomic units (OTUs), accounting for 63.39% of the cecal microbiota of control rats, showed a significant correlation with the total bile acid concentration in HFD-fed rats. A DCA sensitivity test conducted in Firmicutes isolates, corresponding to the predominant OTUs from the HFD-fed rats, exhibited significantly higher DCA resistance compared with Bacteroidetes. The top 12 most abundant OTUs of Firmicutes and Bacteroidetes showing positive or negative correlations with the total bile acid concentration were selected from the HFD-fed rats, and their dynamics were compared with those in the CA-fed rats. Of the 24 OTUs, 18, which constituted 48.28% of the cecal population in the control rats, were altered in the same direction (increase or decrease) in the HFD- and CA-supplemented diet groups. Therefore, approximately half of the cecal populations in the control rats were affected by bile acids, substantiating the bile acid hypothesis microbiologically and quantitatively.

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.

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.

Dysmenorrhea, the most prevalent gynecologic complaint among adolescent females, often has unclear underlying causes. However, it is widely recognized that the accumulation of estrogen and prostaglandins mediates inflammatory responses, leading to uterine ischemia and pelvic pain. Emerging evidence highlights the significant role of intestinal flora as a key regulator of circulating estrogens, linking it to estrogen-modulated diseases. Our laboratory previously demonstrated that sclareol effectively alleviates uterine proliferation and mitigates pain. Nonetheless, the relationship between sclareol's effects and gut microbiota modulation in dysmenorrhea remains unverified. To investigate this, we employed a mouse model induced with high doses of estradiol (1 mg/kg, IP) and administered sclareol (50 mg/kg, gavage) for five days. Fecal samples were subjected to 16S rDNA sequencing to analyze gut microbial composition. While no significant changes in alpha or beta diversity were observed, this study provides pioneering insights into sclareol's impact on specific gut microbiota. Notably, sclareol treatment increased the abundances of Ruminococcus_1, Ruminococcaceae_UCG_013, Ruminococcaceae_UCG_014, and Streptococcus while reducing the abundances of Anaerotruncus and Lactobacillus at the genus level. These effects may be associated with alterations in short-chain fatty acids, β-glucuronidase activity, and overall intestinal health. In conclusion, this study identifies sclareol as a potential functional food candidate for the prevention and management of estrogen-modulated diseases through gut microbiota modulation. Further research is warranted to elucidate the underlying mechanisms and therapeutic applications.

To observe the composition and abundance of the intestinal flora in patients with Wilson disease (WD)-related liver fibrosis and analyze the correlation between the composition of intestinal flora of patients and the evolution of evidence from Chinese medicine, we selected 237 patients with WD-related liver fibrosis and 30 healthy volunteers from the Brain Disease Center of Anhui Provincial Hospital of Chinese Medicine. The patients with WD-related liver fibrosis were divided into 5 groups according to traditional Chinese medicine (TCM) evidence (dampness-heat syndrome, group A; intermingled phlegm and blood stasis syndrome, group B; liver wind stirring up internally syndrome, group C; yin deficiency of the liver and kidney syndrome, group D; and yang deficiency of the spleen and kidney syndrome, group E) and a group healthy volunteers (group F), which served as the control. Stool samples were obtained from the patients in the 6 groups. The 16S rRNA sequencing technique was used to analyze the intestinal flora of the different TCM evidence groups of WD patients and the healthy control group and subjected to a statistical analysis. The intestinal flora abundance was significantly lower in patients with WD-related liver fibrosis than in healthy controls, and the decrease in strain content was more significant in patients with deficiency evidence in groups D and E. In terms of the structure of the phylum-level flora, the Firmicutes phylum was still the dominant phylum, but the contents of the evidence-type groups all decreased, with the most obvious decreases in groups D and E. The results for the Actinobacteria phylum were similar, whereas the opposite was true for the Proteobacteria phylum. The section-level and genus-level results corresponded to the gate level. The intestinal flora of the WD-related liver fibrosis patients and healthy controls differed in terms of abundance and intestinal flora structure, and there were also differences between different Chinese medicine certificates.

Immunoglobulin (Ig) G isotypes in the sera of healthy mice and humans react to commensal bacteria. We previously reported that BALB/c mice with normal gut microbiota possessed abundant B cells that produced IgG2b reactive to commensal bacteria in cecal patches (CePs), indicating a potential source of a systemic pool of commensal bacteria-reactive IgG2b. Mice housed under germ-free conditions demonstrate the importance of the gut microbiota in driving cecal IgG2b responses. However, it is unclear whether the constitutive presence of the gut microbiota and specific bacterial taxa are important for IgG2b responses in adult mice. In this study, we showed that elimination of the gut microbiota by mixed antibiotic treatment in adult mice decreased the abundance of IgG2b⁺ B cells, follicular helper T (Tfh) cells in CePs, and the serum levels of commensal bacteria-reactive IgG2b. Reduced IgG2b responses have also been observed in mice with an altered gut microbiota following treatment with ampicillin or vancomycin. Changes in the diversity and composition of the cecal microbiota, particularly a decrease in Lachnospiraceae, Muribaculaceae, Ruminococcaceae, and Bacteroidaceae abundance at the family level, were observed in these mice. In addition, depletion of CD4⁺ T cells by the injection of neutralizing antibodies in adult mice reduced IgG2b responses. Our results suggest that specific gut bacteria susceptible to ampicillin and vancomycin play roles in providing an abundance of Tfh cells to help the generation of IgG2b⁺ B cells in CePs in adult mice, which may contribute to the supply of systemic commensal bacteria-reactive IgG2b.

Fructobacillus spp. comprise a large genus of fructophilic lactic acid bacteria whose growth characteristics differ from those of other common lactic acid bacteria. The genus has been extensively investigated microbiologically and phylogenetically. However, knowledge regarding Fructobacillus nutritional benefits remains unclear. In particular, Fructobacillus fructosus OS-1010 (OS-1010) was recently shown to act on intestinal cells to release extracellular vesicle exosomes that act on distant target cells. The released exosomes reportedly enhanced the expression of longevity-associated genes and intracellular mitochondrial activity in muscle cells. OS-1010 is expected to be a functional ingredient that improves the function of distant tissues such as muscles and skin upon oral intake. This study examined the effects of the oral intake of heat-killed OS-1010 on human skin in a randomized, double-blind, placebo-controlled, parallel-group study of healthy participants. Significant improvement in skin elasticity was observed after eight weeks of oral OS-1010 intake. Furthermore, although no significant difference was found between the two groups in a wrinkle-related parameter, the OS-1010 group demonstrated improvements in the percentage wrinkle area and overall average wrinkle depth of crow's feet, which were not observed in the placebo group. These results indicate that OS-1010 can contribute to the improvement in skin conditions.

Lactococcus lactis bacterium can be genetically modified to transport the spike protein from SARS-CoV-2, making it a potential candidate for a COVID-19 mucosal vaccine. This study aimed to optimize the nisin concentration, pH, incubation time, and media composition to induce spike protein expression. The concentrations of nisin used in this study ranged from 0 to 40 ng/mL, the incubation period was 3 to 24 hr, and the pH of the growth media ranged from 4 to 8. The media was also supplemented with various yeast extract and sucrose concentrations. The highest protein band intensity was observed at a concentration of 40 ng/mL and an incubation period of 9 hr. Supplementation with 4% w/v yeast extract and 6% w/v sucrose significantly increased the expression of HCR spike protein. In silico simulation suggested a maximal protein band intensity of 70.95 arbitrary units, while the nisin concentration needed to produce half the maximal protein band intensity was estimated to be 9.599 ng/mL. No significant difference in spike protein expression was found between pH variations. The media composition, inducer, and incubation time strongly affect the spike protein expression.

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.