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The mechanism of metabolites produced by lactic acid bacteria in mediating microbial interactions has been difficult to ascertain. This study comparatively evaluated the antimicrobial effect of the novel bacterium Pediococcus acidilactici CCFM18 and explored the global chemical view of its interactions with indicator bacteria. P. acidilactici CCFM18 had sufficiently strong antimicrobial activity to effectively inhibit the growth of the indicator bacteria and enhance their intracellular reactive oxygen species (ROS) level. The emerging technique of matrix-assisted laser desorption ionization–time-of-flight (MALDI-TOF) imaging mass spectrometry indicated that P. acidilactici CCFM18 increased the production of pediocin PA-1 and the penocin A profile during its interaction with the indicator bacteria, thus differing from P. acidilactici CCFM28 (a commonly used laboratory strain). Strikingly, the production of coagulin A was triggered only by signaling molecules made by the competing strain L. thermophilus, suggesting an idiosyncratic response from P. acidilactici CCFM18. Bioinformatic mining of the P. acidilactici CCFM18 draft genome sequence revealed gene loci that code for the complex secondary metabolites analyzed via MSI. Taken together, these results illustrate that chemical interactions between P. acidilactici CCFM18 and indicator bacteria exhibit high complexity and specificity and can drive P. acidilactici CCFM18 to produce different secondary metabolites.

Taurine, an abundant free amino acid, plays multiple roles in the body, including bile acid conjugation, osmoregulation, oxidative stress, and inflammation prevention. Although the relationship between taurine and the gut has been briefly described, the effects of taurine on the reconstitution of intestinal flora homeostasis under conditions of gut dysbiosis and underlying mechanisms remain unclear. This study examined the effects of taurine on the intestinal flora and homeostasis of healthy mice and mice with dysbiosis caused by antibiotic treatment and pathogenic bacterial infections. The results showed that taurine supplementation could significantly regulate intestinal microflora, alter fecal bile acid composition, reverse the decrease in Lactobacillus abundance, boost intestinal immunity in response to antibiotic exposure, resist colonization by Citrobacter rodentium, and enhance the diversity of flora during infection. Our results indicate that taurine has the potential to shape the gut microbiota of mice and positively affect the restoration of intestinal homeostasis. Thus, taurine can be utilized as a targeted regulator to re-establish a normal microenvironment and to treat or prevent gut dysbiosis.

Human gut microbiota interfere with host development and aging. Bifidobacterium is a microbial genus found in the human digestive tract that has probiotic activities such as improving constipation and enhancing immunity. The species and numbers present change with age, but there has been limited research on probiotic gut microbiota at specific ages. This study analyzed the distribution of 610 bifidobacteria in subjects in several age groups (0−17, 18−65, and 66−108 y) using 486 fecal samples and determined the distribution of glycoside hydrolases based on genetic analysis of strains representing 85% of the Bifidobacterium species abundance in each age group. 6’-Sialyllactose is a major component of acidic breast milk oligosaccharides, which can promote human neurogenesis and bifidobacteria growth. Using genotypic and phenotypic association analysis, we investigated the utilization of 6’-sialyllactose by six B. bifidum strains isolated from subjects 0–17 and 18–65 y. A comparative genomic analysis of the six B. bifidum strains revealed differences in genomic features across age groups. Finally, the safety of these strains was evaluated by antibiotic gene and drug resistance phenotype analysis. Our results reveal that the distribution of glycoside hydrolase genes in B. bifidum varies with age, thus affecting the phenotypic results. This provides important insights for the design and application of probiotic products for different ages.

Inflammatory bowel disease (IBD) is a heterogeneous group of diseases associated with chronic inflammation of the intestinal tract, and is highly prevalent worldwide. Although its origin is not yet fully understood, new evidence emphasizes that environmental factors, especially dietary factors and intestinal microbiota disorders are key triggers of IBD. Probiotics, such as Lactobacillaceae spp., play an essential role in human health as they exert beneficial effects on the composition of the human gastrointestinal microbial community and immune system. Probiotic-based therapies have been shown to be effective in alleviating IBD. Among these, Lactobacillaceae rhamnosus is one of the most widely used strains. L. rhamnosus is widely present in the intestines of healthy individuals; it regulates the intestinal immune system and reduces inflammation through a variety of mechanisms. The purpose of this study was to identify scientific evidence related to L. rhamnosus and IBD, review and summarize the results, and discuss the possible mechanisms of action as a starting point for future research on IBD treatment.

Popular edible mushrooms Ganoderma lucidum and Gloeostereum incarnatum can improve physical health as a prebiotic and positively alter intestinal microbiota. Our research investigated the prebiotic effects of Ganoderma lucidum and Gloeostereum incarnatum on colon inflammation through G. lucidum water extraction polysaccharides (GLP), G. incarnatum water extraction polysaccharides (GIP), G. lucidum ethanol extraction (GLE), and G. incarnatum ethanol extraction (GIE) administered in mice after 7 days of dextran sulphate sodium (DSS) administration. Among the extracts, GLE showed reduced mortality rates, prevention of weight loss, mitigated colon length shortening, and decreased disease activity indices and histological scores. COX-2, MPO, and iNOS activities and the inflammatory cytokines’ expressions were determined to demonstrate the inhibition inflammation by GLE. Meanwhile, GLE upregulated the levels of MUC2, ZO-1, claudin-3, and occluding to protect the intestinal barrier. Furthermore, GLE modulated the composition of gut microbiota disturbed by DSS, as it decreased the abundance of Bacteroides, Staphylococcus, and Escherichia_Shigella, and increased Turicibacter and Bifidobacterium. Through cell experiment, GLE had a positive influence on adherens junction, tight junction, and TRAF6/MyD88/NF-κB signaling pathways. In conclusion, GLE supplementation promotes DSS-induced colitis recovery by regulating inflammatory cytokines, preserving the intestinal mucosal barrier, positively modulating microbiota changes, and positively influences immune response in TRAF6/MyD88/NF-κB signaling pathways.

Acute liver injury has multiple causes and can result in liver failure. In this study, we evaluated the hepatoprotective ability of cyanidin (Cy) and investigated its associated mechanisms. Cy administration significantly and dose-dependently ameliorated acute liver injury induced by carbon tetrachloride (CCl4). High-dose Cy showed effects comparable to those achieved by the positive control (silymarin). Severe oxidative stress and inflammatory responses in the liver tissue induced by CCl4 were significantly mitigated by Cy supplementation. The total antioxidant capacity and the activity of superoxide dismutase, catalase, and glutathione peroxidase were increased and the content of malondialdehyde, lipid peroxide, tumor necrosis factor α, interleukin-1β, and interleukin-6 were decreased. Additionally, the Nrf2 and NF-κB signaling pathways, which regulate antioxidative and inflammatory responses, were analyzed using quantitative real-time polymerase chain reaction and western blot assay. Cy treatment not only increased Nrf2 transcription and expression but also decreased NF-κB signaling. Moreover, molecular docking simulation indicated that Cy had high affinity for Keap1 and NF-κB/p65, which may promote nuclear translocation of Nrf2 and inhibit that of NF-κB. In summary, Cy treatment exerted antioxidative and anti-inflammatory effects and ameliorated liver injury by increasing Nrf2 and inhibiting the NF-κB pathway, demonstrating the potential of Cy as a therapeutic agent in liver injury.

Polyethylene glycol (PEG) is one of the most commonly used bowel cleansing methods. Although the safety of PEG for bowel cleansing has been proven, its impact on intestinal microbiota has not been clearly explained, especially in terms of the dynamic changes in intestinal microbiota after PEG bowel cleansing, and there are no consistent results. In this study, stool samples were collected from 12 participants at six time points before and after bowel cleansing. We obtained data on the microbiota of these samples using 16S rRNA gene sequencing and analysis. The data revealed that the structure and composition of the microbiota changed greatly approximately 7 d after intestinal cleansing. The analysis of the dynamic changes in the microbiota showed that the change was most significant at day 3, but the internal structure of the microbiota was similar to that before bowel cleansing. A comparison of the most significantly changed microbiota at different time points before and after bowel cleansing revealed four bacteria: Bacteroides, Roseburia, Eubacterium, and Bifidobacterium. We also established a humanized mouse model to simulate human bowel cleansing using PEG. The results showed that the mouse model achieved similar effects to human bowel cleansing, but its recovery speed was one stage earlier than that of humans. These findings suggest that the intestinal microbiota after bowel cleansing initially underwent a short-term change and then actively returned to its initial status. The results on key bacteria and establishment of mouse models can provide a reference for subsequent research on bowel cleansing.

Under bile salt treatment, strains display significant differences in their tolerance ability, suggesting the existence of diverse resistance mechanisms in Lactobacillus; however, the genes involved in this protective process are not fully understood. In this study, novel target genes associated with bile salt tolerance in Lactobacillus were identified using comparative genomics for PCR detection and the rapid screening of tolerant strains. The bile salt tolerance of 107 lactobacilli isolated from different origins was assessed, and 26 strains with comparatively large differences were selected for further comparative genomic analysis. Tolerant strains had 112 specific genes that were enriched in the phosphotransferase system, the two-component system, carbohydrate metabolism, and the ATP-binding cassette transporter. Six genes from Lactobacillus were cloned into the inducible lactobacillal expression vector pSIP403. Overexpression in the host strain increased its tolerance ability by 11.86–18.08%. The novel genes identified here can be used as targets to design primers for the rapid screening of bile salt-tolerant lactobacilli. Altogether, these results deepen our understanding of bile salt tolerance mechanisms in Lactobacillus and provide a basis for further rapid assessments of tolerant strains.

Limosilactobacillus fermentum is ubiquitous in traditional fermented vegetables, meat products, and the human gut. It is regarded as a “generally recognized as safe” organism by the US Food and Drug Administration. So far, the genetic features and evolutionary strategies of L. fermentum from the human gut and food remain unknown. In this study, comparative genomic analysis of 224 L. fermentum strains isolated from food and human gut (164 L. fermentum strains isolated from human gut was sequenced in our lab) was performed to access genetic diversity and explore genomic features associated with environment. A total of 20,505 gene families were contained by 224 L. fermentum strains and these strains separated mainly into six clades in phylogenetic tree connected with their origin. Food source L. fermentum strains carried more carbohydrate active enzyme genes (belonging to glycosyltransferase family 2, glycoside hydrolase family 43_11, and glycoside hydrolase family 68) compared with that of human gut and L. fermentum derived from food showed higher ability to degrade xylulose and ribose. Moreover, the number of genes encoding otr(A), tetA(46), lmrB, poxtA, and efrB were more abundant in food source L. fermentum, which was consistent with the number of CRISPR spacers and prophages in L. fermentum of food source. This study provides new insight into the adaption of L. fermentum to the food and intestinal tract of humans, suggesting that the genomic evolution of L. fermentum was to some extent driven by environmental stress.

Among the nutrients available to the human gut microbiota, the complex carbohydrates and glycosaminoglycans are important sources of carbon for some of the species of human gut microbiota. Glycosaminoglycan (heparin) from the host is a highly preferred carbohydrate for Bacteroides. To explore how gut microbiota can effectively use heparin as a carbon source for growth, we conducted a screening of the Carbohydrate-Active enzymes (CAZymes) database for lytic enzymes of the PL13 family and Research Center of Food Biotechnology at School of Food Science and Technology of Jiangnan University database of Bacteroides to identify novel glycosaminoglycan-degrading bacterial strains. Four Bacteroides species (Bacteroides eggerthii, Bacteroides clarus, Bacteroides nordii, and Bacteroides finegoldii) that degraded heparin were selected for further studies. Analysis of the polysaccharide utilization sites of the four strains revealed that all of them harbored enzyme encoding genes of the PL13 family. Functional analysis revealed the activity of CAZymes in a medium containing heparin as the sole carbon source, suggesting their potential to degrade heparin and support growth. The four enzymes were heterologous expressed, and their enzymatic properties, kinetics, and thermal stability were determined. The lytic enzyme of B. nordii had high enzymatic activity and thermal stability. The features that cause this high thermal stability were elucidated based on an examination of the three-dimensional structure of the protein. Our findings provide an important theoretical basis for the application of glycosaminoglycans and glycosaminoglycan-degrading enzymes in the medical and biotechnology industries, and an important scientific basis for precision nutrition and medical intervention studies using gut microbiota or enzymes as targets.

Antibiotic-associated diarrhea (AAD) is a self-limiting disease mediated by antibiotic therapy. In clinical practice, several types of probiotics are used in treating AAD, but minimal research has been done on Bacteroides-based microecologics. Our aim was to evaluate the therapeutic effects of Bacteroidetes uniformis FGDLZ48B1, B. intestinalis FJSWX61K18, Bifidobacterium adolescentis FHNFQ48M5, and B. bifidum FGZ30MM3 and their mixture on AAD in mice. The lincomycin hydrochloride-induced AAD models were gavaged with a single strain or a probiotic mixture for a short period to assess the changes in colonic histopathology and cytokine concentrations, intestinal epithelial permeability and integrity, short-chain fatty acids (SCFAs), and the diversity of intestinal microbiota. Our data indicated that both the sole use of Bacteroides and the combination of Bacteroides and Bifidobacterium beneficially weakened systemic inflammation, increased the recovery rate of tissue structures, increased the concentrations of SCFAs, and restored the gut microbiota. Moreover, the probiotic mixture was more effective than the single strain. Specifically, B. uniformis FGDLZ48B1 combined with the B. adolescentis FHNFQ48M5 group was more effective in alleviating the pathological features of the colon, downregulating the concentrations of interleukin (IL)-6, and upregulating the expression of occludin. In summary, our research suggests that administration of a mixture of B. uniformis FGDLZ48B1 and B. adolescentis FHNFQ48M5 is an effective approach for treating AAD.

Lactobacillus salivarius has drawn attention because of its promising probiotic functions. Tolerance to the gastrointestinal tract condition is crucial for orally administrated probiotics to exert their functions. However, previous studies of L. salivarius have only focused on the bile salt resistance of particular strains, without uncovering the common molecular mechanisms of this species. Therefore, in this study, we expanded our research to 90 L. salivarius strains to explore their common functional genes for bile salt resistance. First, the survival rates of the 90 L. salivarius strains in 0.3% bile salt solutions were determined. Comparative genomics analysis was then performed to screen for the potential functional genes related to bile salt tolerance. Next, real-time polymerase chain reaction and gene knockout experiments were conducted to further verify the tolerance-related functional genes. The results indicated that the strain-dependent bile salt tolerance of L. salivarius was mainly associated with four peptidoglycan synthesis-related genes, seven phosphotransferase system-related genes, and one chaperone-encoding gene involved in the stress response. Among them, the GATase1-encoding gene showed the most significant association with bile salt tolerance. In addition, four genes related to DNA damage repair and substance transport were redundant in the strains with high bile salt tolerance. Besides, cluster analysis showed that bile salt hydrolases did not contribute to the bile salt tolerance of L. salivarius. In this study, we determined the global regulatory genes, including LSL_1568, LSL_1716 and LSL_1709, for bile salt tolerance in L. salivarius and provided a potential method for the rapid screening of bile salt-tolerant L. salivarius strains, based on PCR amplification of functional genes.

Increasing attention has been paid to the potential probiotic effects of Latilactobacillus sakei. To explore the genetic diversity of L. sakei, 14 strains isolated from different niches (feces, fermented kimchi, and meat products) and 54 published strains were compared and analyzed. The results showed that the average genome size and GC content of L. sakei were 1.98 Mb and 41.22%, respectively. Its core genome mainly encodes translation and transcription, amino acid synthesis, glucose metabolism, and defense functions. L. sakei has open pan-genomic characteristics, and its pan-gene curve shows an upward trend. The genetic diversity of L. sakei is mainly reflected in carbohydrate utilization, antibiotic tolerance, and immune/competition-related factors, such as clustering regular interval short palindromic repeat sequence (CRISPR)–Cas. The CRISPR system is mainly IIA type, and a few are IIC types. This work provides a basis for the study of this species.

The effectiveness of probiotic consumption in controlling dyslipidemia in type 2 diabetes mellitus (T2DM) has been unclear. We reviewed relevant randomized controlled trials (RCTs) to clarify the effect of probiotic intake on dyslipidemia in T2DM patients. The Web of Science, Scopus, PubMed and Cochrane Library databases were used for searching relevant RCTs published up to October 2020. The total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) concentrations were selected as the primary indicators for dyslipidemia. The results of 13 eligible RCTs showed that probiotic intake could significantly reduce TC (SMD: −0.23, 95% CI: (−0.37, −0.10)) and TG (SMD: −0.27, 95% CI: (−0.44, −0.11)) levels, but did not regulate LDL-C or HDL-C concentrations. Subgroup analysis showed that multispecies probiotics (≥two species), but not single-species probiotics, significantly decreased TC and TG concentrations. Furthermore, powder, but not liquid, probiotics could reduce TC and TG concentrations. This meta-analysis demonstrated that probiotic supplementation is helpful in reducing TC and TG concentrations in T2DM patients. However, more well-controlled trials are needed to clarify the benefits of probiotics on dyslipidemia in T2DM patients.

Latilactobacillus curvatus is a candidate probiotic that has been included in the list of recommended biological agents for certification by the European Food Safety Authority. According to the published genomic information, L. curvatus has several genes that encode metabolic pathways of carbohydrate utilization. In addition, there are some differences in cell surface complex related genes of L. curvatus from different sources. L. curvatus also has several genes that encode bacteriocin production, which can produce Curvacin A and Sakacin P. Due to its ability to produce bacteriocin, it is often used as a bioprotective agent in fermented meat products, to inhibit the growth of a variety of pathogenic and spoilage bacteria. L. curvatus exerts some probiotic effects, such as mediating the production of IL-10 by dendritic cells through NF-κB and extracellular regulated protein kinases (ERK) signals to relieve colitis in mice. This review is the first summary of the genomic and biological characteristics of L. curvatus. Our knowledge on its role in the food industry and human health is also discussed, with the aim of providing a theoretical basis for the development of applications of L. curvatus.