Food and gut originated bacteriocins involved in gut microbe-host interactions.

The gut microbes interact with each other as well as host, influencing human health and some diseases. Many gut commensals and food originated bacteria produce bacteriocins which can inhibit pathogens and modulate gut microbiota. Bacteriocins have comparable narrow antimicrobial spectrum and are attractive potentials for precision therapy of gut disorders. In this review, the bacteriocins from food and gut microbiomes and their involvement in the interaction between producers and gut ecosystem, along with their characteristics, types, biosynthesis, and functions are described and discussed. Bacteriocins are produced by many intestinal commensals and food microbes among which lactic acid bacteria (many are probiotics) has been paid more attention. Bacteriocin production has been generally regarded as a probiotic trait. They give a competitive advantage to bacteria, enabling their colonization in human gut, and mediating the interaction between the producers and host ecosystem. They fight against unwanted bacteria and pathogens without significant impact on the composition of commensal microbiota. Bacteriocins assist the producers to survive and colonize in the gut microbial populations. There is a great need to evaluate and utilize the potential of bacteriocins for improved therapeutic implications for intestinal health.

Nisin Z attenuates lipopolysaccharide-induced mastitis by inhibiting the ERK1/2 and p38 mitogen-activated protein kinase signaling pathways.

Nisin Z is a possible alternative for treating bovine mastitis by inhibiting mastitis-causing pathogens and having anti-inflammatory activity. However, the anti-inflammatory mechanism of nisin Z on mastitis is unknown. Our study aimed to investigate the mechanisms of nisin Z on mastitis. Our results showed that nisin Z inhibited the activation of the ERK1/2 and p38 mitogen-activated protein kinase (MAPK) signaling pathway, decreased the release of pro-inflammatory cytokines (i.e., tumor necrosis factor-α, IL-1ß, and IL-6), and increased the anti-inflammatory cytokine (IL-10) in lipopolysaccharide (LPS)-induced MCF10A cells. After intraperitoneal injection, nisin Z significantly decreased inflammatory cell infiltration in the mammary gland, as well as decreased myeloperoxidase and pro-inflammatory cytokines in serum and mammary gland. Western blot analysis revealed that nisin Z also dramatically suppressed the activation of the ERK1/2 and p38 MAPK signaling pathways in LPS-induced mastitis mice. We also found that nisin Z treatment could enhance the blood-milk barrier. In summary, our study demonstrated that nisin Z exerted an anti-inflammatory effect by inhibiting the ERK1/2 and p38 MAPK signaling pathway and promoting the blood-milk barrier on LPS-induced mastitis.

Probiotic Enterococcus faecalis Symbioflor 1 ameliorates pathobiont-induced miscarriage through bacterial antagonism and Th1-Th2 modulation in pregnant mice.

The bacterium-bacterium interaction between pathogenic and probiotic Enterococcus as well as the bacterium-host interaction between Enterococcus and intestinal epithelium has drawn increasing attentions, but the influence of those interactions on host pregnancy remains largely unexplored. In the present study, we evaluated the effects of probiotic E. faecalis Symbioflor 1 or/and pathogenic E. faecalis OG1RF on the miscarriage of pregnant mice. Using in vitro assays of competition and exclusion and displacement, antagonistic property of E. faecalis Symbioflor 1 against E. faecalis OG1RF was observed, and the former inhibited the translocation of the later in vivo. The rate of miscarriage induced by E. faecalis OG1RF challenge was significantly reduced by 28% with E. faecalis Symbioflor 1 intervention; and the tissue integrity of ileum, colon, uterus, and placenta and placental blood cell density in pregnant mice were drastically improved by such probiotic intervention. Compared with the controls, probiotic intervention significantly upregulated the level of IL-10 and TGF-ß, downregulated levels of IFN-γ, and increased progesterone level that reversed the trend of being Th1 predominance state reported for adverse pregnancy outcome at early pregnancy stage. In conclusion, E. faecalis Symbioflor 1 decreased the translocation of E. faecalis OG1RF, prevented pathogen-induced tissue damage, and changed Th1-Th2 homeostasis toward Th2 predominance during early pregnancy resulting in decreased miscarriage. KEY POINTS: •The mechanism of how probiotic E. faecalis Symbioflor 1 improves pregnancy of mice • Influence of interactions of pathogenic and probiotic Enterococcus on host pregnancy • E. faecalis Symbioflor 1 change Th1-Th2 homeostasis toward Th2 predominance.

Enterococcus faecium WEFA23 from infants lessens high-fat-diet-induced hyperlipidemia via cholesterol 7-alpha-hydroxylase gene by altering the composition of gut microbiota in rats.

Enterococcus faecium WEFA23 is a potential probiotic strain from Chinese infants with the ability to decrease cholesterol levels. Aiming to explore the mechanism of E. faecium WEFA23 in lowering cholesterol in vivo, we examined the gene transcriptions related to cholesterol metabolism, the composition of bile acids in feces, the synthesis of trimethylamine N-oxide (TMAO) in liver, and the composition of the gut microbiota of rats. We found that E. faecium WEFA23 enhanced the synthesis of bile acids by promoting cholesterol excretion, upregulating the genes transcript level relevant to cholesterol decomposition and transportation, and downregulating the genes involved in cholesterol synthesis. In addition, E. faecium WEFA23 not only downregulated the transcript levels of farnesoid X receptor and fibroblast growth factor 15 as well as flavin-containing monooxygenase 3, but also decreased the TMAO production followed by increasing the CYP7A1 transcript level. Furthermore, when orally administered to rats for 35 d, E. faecium WEFA23 improved the gut microbiota diversity of rats fed a high-fat diet. Therein, the ratio of Bacteroidetes to Firmicutes and the abundance of Rikenellaceae increased, whereas the number of Veillonellaceae decreased. These results suggest that reduction of cholesterol level by E. faecium WEFA23 might be related to the changes in the gut microbiota. Our finding provides important information on lowering cholesterol by E. faecium and reveals that Enterococcus spp. might have the potential to decrease the TMAO level.

A Novel Two-Component Bacteriocin, Acidicin P, and Its Key Residues for Inhibiting Listeria monocytogenes by Targeting the Cell Membrane.

Listeria monocytogenes is an important pathogen which easily contaminates food and causes fatal systemic infections in human. Bacteriocins have received much attention regarding their natural methods of controlling health-related pathogens. Here, we investigated and characterized a novel two-component bacteriocin named acidicin P from Pediococcus acidilactici LAC5-17. Acidicin P showed obvious antimicrobial activity to L. monocytogenes. Through a sequence similarity network analysis for two-component bacteriocin precursors mined in the RefSeq database, acidicin P was observed to belong to an unusual group of two-component bacteriocins. Acidicin P contains two peptides designated Adpα and Adpß which are assessed to interact with each other and form a helical dimer structure which can be inserted into the lipid bilayer of target cell membrane. We demonstrate that A5, N7, and G9 in the A5xxxG9 motif of Adpα and S16, R19, and G20 in the S16xxxG20 motif of Adpß played crucial roles in stabilizing the helix-helix interaction of Adpα and Adpß and were essential for the antilisterial activity of acidicin P by site-directed mutagenesis. A positive residue, R14, in Adpα and a negative residue, D12, in Adpß are also important for acidicin P to fight against L. monocytogenes. These key residues are supposed to form hydrogen bonding, which is crucial for the interaction of Adpα and Adpß. Furthermore, acidicin P induces severe permeabilization and depolarization of the cytoplasmic membrane and causes dramatic changes in L. monocytogenes cell morphology and ultrastructure. Acidicin P has the potential to be applied to inhibit L. monocytogenes efficiently both in the food industry and medical treatments. IMPORTANCE L. monocytogenes can cause widespread food contamination and severe human listeriosis, which amount to a large proportion of the public health and economic burdens. Today, L. monocytogenes is usually treated with chemical compounds in the food industry or antibiotics for human listeriosis. Natural and safe antilisterial agents are urgently required. Bacteriocins are natural antimicrobial peptides that have comparable narrow antimicrobial spectra and are attractive potentials for precision therapy for pathogen infection. In this work, we discover a novel two-component bacteriocin designated acidicin P, which shows obvious antilisterial activity. We also identify the key residues in both peptides of acidicin P and demonstrate that acidicin P is inserted into the target cell membrane and disrupts the cell envelop to inhibit the growth of L. monocytogenes. We believe that acidicin P is a promising lead for further development as an antilisterial drug.

Exploring the bacterial community succession and metabolic profiles of Lonicera japonica Thunb. residues during anaerobic fermentation.

Discarding Lonicera japonica Thunb. (LJT) residues containing many active metabolites create tremendous waste. This study aimed to effectively use LJT residues by anaerobic fermentation. Fermentation significantly decreased the pH values and reduced the abundance of undesirable bacteria (potential pathogenic and biofilm-forming) while increasing Lactobacillus abundance. Compound additive use further improved fermentation quality (significantly increased the lactic acid (LA) content and decreased the pH values and ammonia nitrogen (a-N) content) and nutrient quality (significantly decreased the acid detergent fiber (ADF) content and increased the water-soluble carbohydrate (WSC) content) and optimized the microbial community (increased the Lactobacillus abundance). Fermentation also altered the flavonoids, alkaloids and phenols contents in the residues with minor effects on the functional metabolites amounts. The LJT residues metabolic profile was mainly attributed to its epiphytic bacteria, with a small contribution from the compound additive. Thus, compound additives may improve anaerobic LJT residue fermentation without functionally impairing the metabolites.

Modulation of Fermentation Quality and Metabolome in Co-ensiling of Sesbania cannabina and Sweet Sorghum by Lactic Acid Bacterial Inoculants.

Sesbania cannabina (SC) is a protein-rich roughage that thrives under moderate-severe saline-alkali (MSSA) soils with the potential to relieve the shortage of high nutritive forage. Sweet sorghum (SS) also tolerates MSSA soils and contains rich fermentable carbohydrates which could improve the fermentation quality in mixed silage. The present study investigated the silage quality, bacterial community, and metabolome in the mixed silage of SC and SS (SC-SS) with or without lactic acid bacterial (LAB) inoculants. Four ratios (10:0, 7:3, 5:5, and 3:7) of SC and SS were treated with sterile water or LAB inoculants (homofermentative Companilactobacillus farciminis and Lactiplantibacillus plantarum, and heterofermentative Lentilactobacillus buchneri and Lentilactobacillus hilgardii), which were analyzed after 60 days of ensiling. Results revealed that LAB inoculation improved the fermentation quality by increasing the lactic acid content and decreasing the ammonia nitrogen and butyric acid contents compared with the untreated group. LAB inoculation also raised the relative feed value by reducing indigestible fibers [e.g., neutral detergent fiber (NDF), acid detergent fiber, and hemicellulose]. Microbial and metabolomic analysis indicated that LAB inoculants could modify the bacterial community and metabolome of SC-SS silage. In co-ensiling samples except for SC alone silage, L. buchneri and L. hilgardii were the dominant species. Metabolites with bioactivities like anti-inflammatory, antioxidant, antimicrobial, and anti-tumor were upregulated with LAB inoculation. Furthermore, correlation analysis demonstrated that active metabolites (e.g., glycitin, glabrene, alnustone, etc.) were positively correlated with L. buchneri, while tripeptides (e.g., SPK, LLK, LPH, etc.) were positively correlated with L. hilgardii. Adequately describing the SC-SS silage by multi-omics approach might deepen our understanding of complicated biological processes underlying feature silages fermentation. Moreover, it may also contribute to screening of targeted functional strains for MSSA-tolerating forage to improve silage quality and promote livestock production.

High-throughput discovery of novel lanthipeptides and producers by metagenomic mining of isolates population (MMIP) from Chinese spicy cabbage.

Lanthipeptides are known antimicrobial agents having great potential for application in food preservation. Many lanthipeptide biosynthetic gene clusters (BGCs) were mined in fermented food microbiota, however, it is difficult to obtain the bioactive lanthipeptides and their producing strains. Here, we established a high-throughput strategy designated Metagenomic Mining of Isolates Population (MMIP) to efficiently excavate and obtain novel lanthipeptides, especially their potential producing strains. MMIP procedure involves gathering bacteria isolates using culturable strategy, metagenomic mining for lanthipeptides and screening their producers, and characterization of specific lanthipeptides. 928 biosynthetic gene clusters including 139 ribosomally synthesized and post-translationally modified peptides (RiPPs) gene clusters were discovered in the metagenomic data of the isolates by antiSMASH. Entianin, lactocin S, lichenicidin, and 17 novel lanthipeptides gene clusters corresponding to 29 possible producers were further found from the harvested isolates population. Entianin and a novel two-component lanthipeptide paralicin were purified from Bacillus subtilis C5B1 and Bacillus paralicheniformis BaC1-8, respectively. They showed strong inhibitory activity to food spoilage bacteria Bacillus cereus and Listeria monocytogenes, and have great potential for application in food preservation. A novel lanthipeptide polysacin was also obtained using semi-in vitro biosynthesis. MMIP affords a novel strategy for effectively excavating lanthipeptides, especially their producers from diverse environmental niches.

Dynamic Changes in Fermentation Quality and Structure and Function of the Microbiome during Mixed Silage of Sesbania cannabina and Sweet Sorghum Grown on Saline-Alkaline Land.

Protein-rich Sesbania cannabina and sugar-rich sweet sorghum [Sorghum dochna (Forssk.) Snowden] are characterized by their higher tolerance to saline-alkaline stresses and simultaneous harvests. They could be utilized for coensiling because of their nutritional advantages, which are crucial to compensate protein-rich forage in saline-alkaline regions. The current study investigated the fermentation quality, microbial community succession, and predicted microbial functions of Sesbania cannabina and sweet sorghum in mixed silage during the fermentation process. Before ensiling, the mixtures were treated with compound lactic acid bacteria (LAB) inoculants followed by 3, 7, 14, 30, and 60 days of fermentation. The results revealed that the inoculated homofermentative species Lactobacillus plantarum and Lactobacillus farciminis dominated the early phase of fermentation, and these shifted to the heterofermentative species Lactobacillus buchneri and Lactobacillus hilgardii in the later phase of fermentation. As a result, the pH of the mixed silages decreased significantly, accompanied by the growth of acid-producing microorganisms, especially L. buchneri and L. hilgardii, which actively influenced the bacterial community structure and metabolic pathways. Moreover, the contents of lactic acid, acetic acid, 1,2-propanediol, and water-soluble carbohydrates increased, while the contents of ammonia-N and fiber were decreased, with increasing ratios of sweet sorghum in the mixed silage. Overall, coensiling Sesbania cannabina with >30% sweet sorghum is feasible to attain high-quality silage, and the relay action between homofermentative and heterofermentative LAB species could enhance fermentation quality and conserve the nutrients of the mixed silage. IMPORTANCE The coensiling of Sesbania cannabina and sweet sorghum is of great practical importance in order to alleviate the protein-rich forage deficiency in saline-alkaline regions. Furthermore, understanding the microbial community's dynamic changes, interactions, and metabolic pathways during ensiling will provide the theoretical basis to effectively regulate silage fermentation. Here, we established that coensiling Sesbania cannabina with >30% sweet sorghum was effective at ensuring better fermentation quality and preservation of nutrients. Moreover, the different fermentation types of LAB strains played a relay role during the fermentation process. The homofermentative species L. plantarum and L. farciminis dominated in the early phase of fermentation, while the heterofermentative species L. buchneri and L. hilgardii dominated in the later phase of fermentation. Their relay action in Sesbania cannabina-sweet sorghum mixed silage may help to improve fermentation quality and nutrient preservation.

Influence of Lactobacillus plantarum inoculation on the silage quality of intercropped Lablab purpureus and sweet sorghum grown in saline-alkaline region.

Ensiling legume with cereal is an effective method to ensure the energy rich-feed, but no information is available on the microbial fermentation mechanism of intercropped Lablab purpureus (Lablab) and sweet sorghum in the saline-alkaline region. Therefore, the present study investigated the silage quality and microbial community of intercropped Lablab and sweet sorghum silages grown in the saline-alkaline region with or without inoculation of Lactobacillus plantarum (LP). The experimental treatments were prepared according to the Lablab and sweet sorghum planting patterns: Lablab and sweet sorghum sowing seed ratios were 1:1 (L), 5:1 (M), and 9:1 (H). After harvesting, each mixture was treated with LP or sterilized water (CK), followed by 60 days of fermentation. Results showed that both LP inoculation and intercropping significantly raised the lactic acid (LA) content and decreased the pH value, acetic acid (AA), and ammonia-N in intercropped silages. The LP addition and intercropping also improved the relative feed value by reducing structural carbohydrates. Moreover, LP silages had a greater relative abundance of Lactobacillus than CK silages, and its relative abundance increased with an increased seed-sowing ratio of Lablab in intercropping. LP was the prevalent species in LP silages compared to CK silages, and its relative abundance also increased with an increased seed-sowing ratio of Lablab in intercropping. The genus Lactobacillus was negatively correlated with ammonia-N (R = -0.6, p = 0.02) and AA (R = -0.7, p < 0.01) and positively correlated with LA (R = 0.7, p < 0.01) and crude protein (R = 0.6, p = 0.04). Overall, the intercropped seeding ratios of Lablab and sweet sorghum of ≥ 5:1 with LP inoculation resulted in better fermentation quality and preservation of nutritional components providing theoretical support and guidance for future intercropped protein-rich silage production in the saline-alkaline region.

Bacteriocins: Potential for Human Health.

Due to the challenges of antibiotic resistance to global health, bacteriocins as antimicrobial compounds have received more and more attention. Bacteriocins are biosynthesized by various microbes and are predominantly used as food preservatives to control foodborne pathogens. Now, increasing researches have focused on bacteriocins as potential clinical antimicrobials or immune-modulating agents to fight against the global threat to human health. Given the broad- or narrow-spectrum antimicrobial activity, bacteriocins have been reported to inhibit a wide range of clinically pathogenic and multidrug-resistant bacteria, thus preventing the infections caused by these bacteria in the human body. Otherwise, some bacteriocins also show anticancer, anti-inflammatory, and immune-modulatory activities. Because of the safety and being not easy to cause drug resistance, some bacteriocins appear to have better efficacy and application prospects than existing therapeutic agents do. In this review, we highlight the potential therapeutic activities of bacteriocins and suggest opportunities for their application.