Screening canine sources for novel antimicrobials reveals the circular broad-spectrum bacteriocin, caledonicin, produced by Staphylococcus caledonicus.

Introduction: Antimicrobial-resistant pathogens present an ongoing threat to human and animal health, with deaths linked to antimicrobial resistance (AMR) predicted to increase annually. While the misuse and overuse of antibiotics in humans undoubtedly contribute to this escalation, antibiotic use in the veterinary field, including companion animals, also plays a contributing role. Pet owners' desire to improve the quality of life of their pets is likely to support antibiotic use in this field. Consequently, there is a need for antibiotic alternatives to treat bacterial infections. This study set out to screen for antimicrobial peptides known as bacteriocins from bacterial isolates of aerobic/microaerophilic environments of canine sources and determine their potential as antibiotic alternatives against clinically relevant pathogens. Methods: Following a laboratory-based protocol, 22 bacterial isolates were subjected to whole-genome sequencing (WGS), and a total of 14 putative novel bacteriocins were identified from both class I and II bacteriocin classes. One particular bacteriocin, herein named caledonicin, was identified via in silico analysis from a Staphylococcus caledonicus strain and partially purified for further in vitro evaluation. Results: Caledonicin is a 64-amino acid (IAANLGVSSGTAYS MANALNNISNVATA LTIIGTFTGVGTIGSGIA ATILAILKKKGVAAAAAF) novel circular bacteriocin most closely related to enterocin_NKR-5-3B based on core peptide alignment (39.1%), with a molecular weight of 6077.1 Da. Caledonicin exhibits a broad-spectrum of activity against a range of pathogenic bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), methicillin-resistant Staphylococcus pseudintermedius (MRSP), and Listeria monocytogenes; and the gut-related bacterium associated with Crohn's disease, Mediterraneibacter gnavus ATCC 29149 (previously Ruminococcus gnavus ATCC 29149). Discussion: This represents the first bacteriocin screening study involving bacteria from canine sources and confirms this is a rich environment for bacteriocin-producing strains. This study also identifies and characterises the first novel bacteriocin from the staphylococcal species, Staphylococcus caledonicus.

Lactobacillus plantarum Ameliorates Colorectal Cancer by Ameliorating the Intestinal Barrier through the CLA-PPAR-γ Axis.

Colorectal cancer (CRC) is the third-largest cancer worldwide. Lactobacillus can regulate the intestinal barrier and gut microbiota. However, the mechanisms of Lactobacillus that alleviate CRC remained unknown. This study aimed to explore the regulatory effect of Lactobacillus plantarum on CRC and its potential mechanism. CCFM8661 treatment significantly ameliorated CRC compared with phosphate-buffered solution (PBS) treatment in ApcMin/+ mice. In addition, conjugated linoleic acid (CLA) was proved to be the key metabolite for CCFM8661 in ameliorating CRC by molecular biology techniques. Peroxisome proliferator-activated receptor γ (PPAR-γ) was proved to be the key receptor in ameliorating CRC by inhibitor intervention experiments. Moreover, supplementation with CCFM8661 ameliorated CRC by producing CLA to inhibit NF-κB pathway and pro-inflammatory cytokines, up-regulate ZO-1, Claudin-1, and MUC2, and promote tumor cell apoptosis in a PPAR-γ-dependent manner. Metagenomic analysis showed that CCFM8661 treatment significantly increased Odoribacter splanchnicus, which could ameliorate CRC by repairing the intestinal barrier. Clinical results showed that intestinal CLA, butyric acid, PPAR-γ, and Lactobacillus were significantly decreased in CRC patients, and these indicators were significantly negatively correlated with CRC. CCFM8661 alleviated CRC by ameliorating the intestinal barrier through the CLA-PPAR-γ axis. These results will promote the development of dietary probiotic supplements for CRC.

Isolation and characterization of Septuagintavirus; a novel clade of Escherichia coli phages within the subfamily Vequintavirinae.

Escherichia coli is a commensal inhabitant of the mammalian gut microbiota, frequently associated with various gastrointestinal diseases. There is increasing interest in comprehending the variety of bacteriophages (phages) that target this bacterium, as such insights could pave the way for their potential use in therapeutic applications. Here, we report the isolation and characterization of four newly identified E. coli infecting tailed phages (W70, A7-1, A5-4, and A73) that were found to constitute a novel genus, Septuagintavirus, within the subfamily Vequintavirinae. Genomes of these phages ranged from 137 kbp to 145 kbp, with a GC content of 41 mol%. They possess a maximum nucleotide similarity of 30% with phages of the closest phylogenetic genus, Certrevirus, while displaying limited homology to other genera of the Vequintavirinae family. Host range analysis showed that these phages have limited activity against a panel of E. coli strains, infecting 6 out of 16 tested isolates, regardless of their phylotype. Electrospray ionization-tandem mass spectrometry (ESI-MS/MS) was performed on the virion of phage W70, allowing the identification of 28 structural proteins, 19 of which were shared with phages of other genera of Vequintavirinae family. The greatest diversity was identified with proteins forming tail fiber structures, likely indicating the adaptation of virions of each phage genus of this subfamily for the recognition of their target receptor on host cells. The findings of this study provide greater insights into the phages of the subfamily Vequintavirinae, contributing to the pool of knowledge currently known about these phages. IMPORTANCE: Escherichia coli is a well-known bacterium that inhabits diverse ecological niches, including the mammalian gut microbiota. Certain strains are associated with gastrointestinal diseases, and there is a growing interest in using bacteriophages, viruses that infect bacteria, to combat bacterial infections. Here, we describe the isolation and characterization of four novel E. coli bacteriophages that constitute a new genus, Septuagintavirus, within the subfamily Vequintavirinae. We conducted mass spectrometry on virions of a representative phage of this novel clade and compared it to other phages within the subfamily. Our analysis shows that virion structure is highly conserved among all phages, except for proteins related to tail fiber structures implicated in the host range. These findings provide greater insights into the phages of the subfamily Vequintavirinae, contributing to the existing pool of knowledge about these phages.

Raffinocyclicin is a novel plasmid-encoded circular bacteriocin produced by Lactococcus raffinolactis with broad-spectrum activity against many gram-positive food pathogens.

This study describes the discovery and characterization of raffinocyclicin, a novel plasmid-encoded circular bacteriocin, produced by the raw milk isolate Lactococcus raffinolactis APC 3967. This bacteriocin has a molecular mass of 6,092 Da and contains 61 amino acids with a three-amino acid leader peptide. It shows the highest identity to the circular bacteriocins bacicyclicin XIN-1 (42.62%), aureocyclicin 4185 (42.62%), and garvicin ML (41.53%). A broad inhibitory spectrum includes strains from Staphylococcus, Enterococcus, Streptococcus, Micrococcus, Lactobacillus, Leuconostoc, and Listeria, in addition to a pronounced inhibitory effect against Lactococcus and Clostridium. It displays low sensitivity to trypsin, most likely as a result of its circular nature. The raffinocyclicin gene cluster is composed of 10 genes: 6 core genes, genes encoding an accessory three-component ABC transporter (rafCDE), and a putative transcriptional regulator related to the MutR family. A lack of inhibitory activity in the cell-free supernatant combined with the pronounced activity of cell extracts suggests that the majority of raffinocyclicin is associated with the cell rather than being released to the extracellular environment. This is the first report of a bacteriocin produced by the L. raffinolactis species.IMPORTANCEThe present study aimed to characterize raffinocyclicin, a novel circular bacteriocin produced by the lactic acid bacteria Lactococcus raffinolactis APC 3967. Bacteriocins are generally cationic and hydrophobic peptides with antimicrobial activity, which present diverse biotechnological properties of interest for the food industry. Raffinocyclicin inhibits a wide range of bacteria, including foodborne pathogens, and is stable against different treatments which suggest its potential as a natural biopreservative. Whole-genome sequencing and the genetic analysis of the raffinocyclicin gene cluster showed that it is encoded by plasmid that could be used in the future to transfer the ability to produce the bacteriocin to other lactic acid bacteria for industrial applications. These results together highlight the potential of this novel antimicrobial as a biopreservative to be used by the food industry.

Somatic cell count as an indicator of subclinical mastitis and increased inflammatory response in asymptomatic lactating women.

Subclinical mastitis is an asymptomatic inflammatory condition that can be difficult to define and diagnose. In the dairy industry, subclinical mastitis is diagnosed by milk somatic cell counts (SCCs) of ≥250,000 cells mL-1. In this pilot study, we assessed the efficacy of this index to identify human subclinical mastitis by comparing SCC levels with the inflammatory response [interleukin-8 (IL-8) levels] in 37 samples from asymptomatic and 10 clinical mastitis (CM) lactating women. The milk microbiota was determined by 16S rRNA gene sequencing. The SCC of CM samples ranged from 310,000 to 6,600,000 cells mL-1. However, 14 of 37 (37.8%) asymptomatic samples had high SCC (250,000-460,000 cells mL-1), indicating subclinical mastitis. SCC levels significantly (P < 0.001) and positively correlated with milk IL-8 levels reflecting the escalating inflammatory response across subclinical and clinical mastitis samples. Samples with an SCC of ≥250,000 cells mL-1 showed significant increases in IL-8 responses when compared with milk samples from healthy women. The milk microbiome of CM samples was dominated by streptococcal and staphylococcal species (89.9% combined median relative abundance). In contrast, the combined median streptococcal/staphylococcal relative levels were 75.4% and 66.3% in milks from asymptomatic (subclinical mastitis) and healthy groups, respectively. The Streptococcus genus was increased in samples with an SCC of ≥250,000, although this should be interpreted with caution. Thus, the index of ≥250,000 somatic cells mL-1 could be a reliable indicator of subclinical mastitis in humans and should aid future studies investigating the impact of subclinical mastitis on maternal health, breastfeeding behaviors, infant health, and development. IMPORTANCE: This pilot study suggests that SCC at a level of (greater than or equal to) 250,000 cells mL-1, as used in the dairy industry, is a suitable index to identify asymptomatic subclinical mastitis in lactating women since it reflects a significant increase in the inflammatory response compared to milk samples from healthy women. Using this index should aid studies into the short- and long-term consequences of subclinical mastitis for mother and infant.

The interplay between diet and the gut microbiome: implications for health and disease.

Diet has a pivotal role in shaping the composition, function and diversity of the gut microbiome, with various diets having a profound impact on the stability, functionality and diversity of the microbial community within our gut. Understanding the profound impact of varied diets on the microbiome is crucial, as it will enable us not only to make well-informed dietary decisions for better metabolic and intestinal health, but also to prevent and slow the onset of specific diet-related diseases that stem from suboptimal diets. In this Review, we explore how geographical location affects the gut microbiome and how different diets shape its composition and function. We examine the mechanisms by which whole dietary regimes, such as the Mediterranean diet, high-fibre diet, plant-based diet, high-protein diet, ketogenic diet and Western diet, influence the gut microbiome. Furthermore, we underscore the need for exhaustive studies to better understand the causal relationship between diet, host and microorganisms for the development of precision nutrition and microbiome-based therapies.

The Marine Fish Gut Microbiome as a Source of Novel Bacteriocins.

The marine environment is the largest ecological habitat on Earth, albeit one of the least explored, particularly in terms of its microbial inhabitants. The marine fish gut is host to a diverse microbial community from which diverse bioactive molecules can be sourced. Due to the unique environmental pressures these microbial communities experience, the bioactive molecules they produce often evolve unique adaptations that give them diverse structures and activities, differentiating them from terrestrial homologues. Of particular interest, due to their structural and functional diversity, are the ribosomally-synthesized antimicrobial peptides (bacteriocins). With increasing pressure from emerging antibiotic-resistant disease and industrial demand for novel therapeutics, the marine fish gut microbiome represents a relatively untapped resource of novel bacteriocins that could prove beneficial to human health and aquaculture. This review presents an overview of the marine fish gut microbiome and explores its potential as a source of bacteriocins for human health with considerations for applications and future research in this area.

Bifidobacterium longum subsp. infantis regulates Th1/Th2 balance through the JAK-STAT pathway in growing mice.

Objectives: Bifidobacterium longum subsp. infantis is a dominant bacterium in infant gut, which plays a critical role in maintaining the health and development of infants. This study investigated the abilities of eight different strains of B. longum subsp. infantis to regulate the T helper (Th)1/Th2 balance. Methods: Eight B. longum subsp. infantis strains, including I2MI (FJSWXI2MIM1), I4MI [FJSWXI4MI (CCFM1270)], I4MNI (FJSWXI4MNIM1), I5TI (FJSWXI5TIM1), I6TI (FJSWXI6TIM1), I8TI [FJSWXI8TI (CCFM1271)], I10TI [FJSWXI10TI (CCFM1272)], and B6MNI [BJSWXB6MNIM1 (CCFM1269)], were gavaged to BALB/C pups in both female (n = 8) and male (n = 8) mice starting from 1 to 3 weeks old (1 × 109 CFU/day/mice). Selected immune cells were assessed by immunofluorescence and flow cytometry. Cytokines and immunoglobulins were determined by ELISA. Bacterial and bifidobacterial communities were determined by 16S rRNA gene sequencing and bifidobacterial groEL sequencing. Results: B. longum subsp. infantis I4MI and I8TI were shown to increase the ration of colonic IgG2a/IgE in male mice (P < 0.05). B6MNI was demonstrated to significantly increase the levels of colonic IFN-γ and IgG2a, as well as the ratio of IgG2a/IgE in female mice (P < 0.05). It was also shown to significantly increase the ratio of colonic IgG2a/IgE (P < 0.05) and reduce the level of colonic IL-4 in male mice (P < 0.05). Furthermore, B6MNI was demonstrated to regulate colonic JAK/STAT pathway in both male and female mice. I4MI, I5TI, and B6MNI were shown to increase the relative abundance of Bifidobacterium and B. longum subsp. infantis in both male and female mice, whereas I8TI was only shown to increase the relative abundance of Bifidobacterium and B. longum subsp. infantis in male mice (P < 0.05). Conclusion: These results indicated supplementation with B. longum subsp. infantis in early infancy may regulate the Th1/Th2 immune balance, which may prevent the development of related diseases.

Probiotic intervention improves metabolic outcomes in gestational diabetes mellitus: A meta-analysis of randomized controlled trials.

AIMS: To conduct a randomized controlled trial meta-analysis and provide concise and specific recommendations for clinical practice optimization of gestational diabetes for probiotics. METHODS: Up until May 2023, we conducted a thorough, systematic search of PubMed, Cochrane Central Controlled Trials, and Embase. Stata software was used to merge the resulting data from the original studies. Cochran's Q and the I2 statistics were used to evaluate and quantify heterogeneity. The GRADE method was used to evaluate the overall quality of the evidence. Sources of heterogeneity were analyzed through a leave-one-out meta-analysis, a Galbraith plot, and a subgroup analysis. RESULTS: A meta-analysis of 11 randomized controlled trials with a total of 713 participants was finally conducted. Our findings indicated the administration of probiotics at a median dosage of 6 × 109 CFU/day led to a substantial improvement in fasting glucose levels (MD: -4.16 mg/dL [95% CI: -6.78, -1.54]; P < 0.001), fasting insulin levels (MD: -3.33 µIU/ml [95% CI: -4.92, -1.74]; P < 0.001), homeostatic model assessment for insulin resistance (HOMA-IR) (MD: -0.71 [95% CI: -0.97, -0.45]; P < 0.001), and quantitative insulin sensitivity check index (QUICKI) (MD: 0.01 [95% CI: 0.01, 0.02]; P < 0.001). Subgroup analysis indicated that probiotic intervention exerted a more significant reduction in fasting blood glucose in patients with higher baseline BMI and glucose levels, and reduced fasting insulin more markedly in those with elevated baseline insulin. According to the GRADE assessment, the quality of evidence for fasting blood glucose and QUICKI was rated as "high", while the quality for fasting insulin and HOMA-IR was rated as "moderate". CONCLUSIONS: Probiotic intervention has been shown to significantly decrease levels of fasting blood glucose, fasting insulin, and HOMA-IR, while elevating QUICKI levels in patients with GDM, underscoring the potential utility of probiotics in the adjunctive management of GDM.

Bacteriocin diversity, function, discovery and application as antimicrobials.

Bacteriocins are potent antimicrobial peptides that are produced by bacteria. Since their discovery almost a century ago, diverse peptides have been discovered and described, and some are currently used as commercial food preservatives. Many bacteriocins exhibit extensively post-translationally modified structures encoded on complex gene clusters, whereas others have simple linear structures. The molecular structures, mechanisms of action and resistance have been determined for a number of bacteriocins, but most remain incompletely characterized. These gene-encoded peptides are amenable to bioengineering strategies and heterologous expression, enabling metagenomic mining and modification of novel antimicrobials. The ongoing global antimicrobial resistance crisis demands that novel therapeutics be developed to combat infectious pathogens. New compounds that are target-specific and compatible with the resident microbiota would be valuable alternatives to current antimicrobials. As bacteriocins can be broad or narrow spectrum in nature, they are promising tools for this purpose. However, few bacteriocins have gone beyond preclinical trials and none is currently used therapeutically in humans. In this Review, we explore the broad diversity in bacteriocin structure and function, describe identification and optimization methods and discuss the reasons behind the lack of translation beyond the laboratory of these potentially valuable antimicrobials.

Exopolysaccharides Produced by Bifidobacterium longum subsp. longum YS108R Ameliorates DSS-Induced Ulcerative Colitis in Mice by Improving the Gut Barrier and Regulating the Gut Microbiota.

Ulcerative colitis (UC) is a major disease that has endangered human health. Our previous study demonstrated that Bifidobacterium longum subsp. longum YS108R, a ropy exopolysaccharide (EPS)-producing bacterium, could alleviate UC in mice, but it is unclear whether EPS is the key substance responsible for its action. In this study, we proposed to investigate the remitting effect of EPS from B. longum subsp. longum YS108R on UC in a DSS-induced UC mouse model. Water extraction and alcohol precipitation were applied to extract EPS from the supernatant of B. longum subsp. longum YS108R culture. Then the animal trial was performed, and the results indicated that YS108R EPS ameliorated colonic pathological damage and the intestinal barrier. YS108R EPS suppressed inflammation via NF-κB signaling pathway inhibition and attenuated oxidative stress via the Nrf2 signaling pathway activation. Remarkably, YS108R EPS regulated gut microbiota, as evidenced by an increase in short-chain fatty acid (SCFA)-producing bacteria and a decline in Gram-negative bacteria, resulting in an increase of propionate and butyrate and a reduction of lipopolysaccharide (LPS). Collectively, YS108R EPS manipulated the intestinal microbiota and its metabolites, which further improved the intestinal barrier and inhibited inflammation and oxidative stress, thereby alleviating UC.

Promiscuous, persistent and problematic: insights into current enterococcal genomics to guide therapeutic strategy.

Vancomycin-resistant enterococci (VRE) are major opportunistic pathogens and the causative agents of serious diseases, such as urinary tract infections and endocarditis. VRE strains mainly include species of Enterococcus faecium and E. faecalis which can colonise the gastrointestinal tract (GIT) of patients and, following growth and persistence in the gut, can transfer to blood resulting in systemic dissemination in the body. Advancements in genomics have revealed that hospital-associated VRE strains are characterised by increased numbers of mobile genetic elements, higher numbers of antibiotic resistance genes and often lack active CRISPR-Cas systems. Additionally, comparative genomics have increased our understanding of dissemination routes among patients and healthcare workers. Since the efficiency of currently available antibiotics is rapidly declining, new measures to control infection and dissemination of these persistent pathogens are urgently needed. These approaches include combinatory administration of antibiotics, strengthening colonisation resistance of the gut microbiota to reduce VRE proliferation through commensals or probiotic bacteria, or switching to non-antibiotic bacterial killers, such as bacteriophages or bacteriocins. In this review, we discuss the current knowledge of the genomics of VRE isolates and state-of-the-art therapeutic advances against VRE infections.

Early life exposure of infants to benzylpenicillin and gentamicin is associated with a persistent amplification of the gut resistome.

BACKGROUND: Infant gut microbiota is highly malleable, but the long-term longitudinal impact of antibiotic exposure in early life, together with the mode of delivery on infant gut microbiota and resistome, is not extensively studied. METHODS: Two hundred and eight samples from 45 infants collected from birth until 2 years of age over five time points (week 1, 4, 8, 24, year 2) were analysed. Based on shotgun metagenomics, the gut microbial composition and resistome profile were compared in the early life of infants divided into three groups: vaginal delivery/no-antibiotic in the first 4 days of life, C-section/no-antibiotic in the first 4 days of life, and C-section/antibiotic exposed in first 4 days of life. Gentamycin and benzylpenicillin were the most commonly administered antibiotics during this cohort's first week of life. RESULTS: Newborn gut microbial composition differed in all three groups, with higher diversity and stable composition seen at 2 years of age, compared to week 1. An increase in microbial diversity from week 1 to week 4 only in the C-section/antibiotic-exposed group reflects the effect of antibiotic use in the first 4 days of life, with a gradual increase thereafter. Overall, a relative abundance of Actinobacteria and Bacteroides was significantly higher in vaginal delivery/no-antibiotic while Proteobacteria was higher in C-section/antibiotic-exposed infants. Strains from species belonging to Bifidobacterium and Bacteroidetes were generally persistent colonisers, with Bifidobacterium breve and Bifidobacterium bifidum species being the major persistent colonisers in all three groups. Bacteroides persistence was dominant in the vaginal delivery/no-antibiotic group, with species Bacteroides ovatus and Phocaeicola vulgatus found to be persistent colonisers in the no-antibiotic groups. Most strains carrying antibiotic-resistance genes belonged to phyla Proteobacteria and Firmicutes, with the C-section/antibiotic-exposed group presenting a higher frequency of antibiotic-resistance genes (ARGs). CONCLUSION: These data show that antibiotic exposure has an immediate and persistent effect on the gut microbiome in early life. As such, the two antibiotics used in the study selected for strains (mainly Proteobacteria) which were multiple drug-resistant (MDR), presumably a reflection of their evolutionary lineage of historical exposures-leading to what can be an extensive and diverse resistome. Video Abstract.

Harnessing the endogenous Type I-C CRISPR-Cas system for genome editing in Bifidobacterium breve.

Bifidobacterium breve, one of the main bifidobacterial species colonizing the human gastrointestinal tract in early life, has received extensive attention for its purported beneficial effects on human health. However, exploration of the mode of action of such beneficial effects exerted by B. breve is cumbersome due to the lack of effective genetic tools, which limits its synthetic biology application. The widespread presence of CRISPR-Cas systems in the B. breve genome makes endogenous CRISPR-based gene editing toolkits a promising tool. This study revealed that Type I-C CRISPR-Cas systems in B. breve can be divided into two groups based on the amino acid sequences encoded by cas gene clusters. Deletion of the gene coding uracil phosphoribosyl-transferase (upp) was achieved in five B. breve strains from both groups using this system. In addition, translational termination of uracil phosphoribosyl-transferase was successfully achieved in B. breve FJSWX38M7 by single-base substitution of the upp gene and insertion of three stop codons. The gene encoding linoleic acid isomerase (bbi) in B. breve, being a characteristic trait, was deleted after plasmid curing, which rendered it unable to convert linoleic acid into conjugated linoleic acid, demonstrating the feasibility of successive editing. This study expands the toolkit for gene manipulation in B. breve and provides a new approach toward functional genome editing and analysis of B. breve strains.IMPORTANCEThe lack of effective genetic tools for Bifidobacterium breve is an obstacle to studying the molecular mechanisms of its health-promoting effects, hindering the development of next-generation probiotics. Here, we introduce a gene editing method based on the endogenous CRISPR-Cas system, which can achieve gene deletion, single-base substitution, gene insertion, and successive gene editing in B. breve. This study will facilitate discovery of functional genes and elucidation of molecular mechanisms of B. breve pertaining to health-associated benefits.

Isolation and characterization of a novel lytic Parabacteroides distasonis bacteriophage φPDS1 from the human gut.

The human gut microbiome plays a significant role in health and disease. The viral component (virome) is predominantly composed of bacteriophages (phages) and has received significantly less attention in comparison to the bacteriome. This knowledge gap is largely due to challenges associated with the isolation and characterization of novel gut phages, and bioinformatic hurdles such as the lack of a universal phage marker gene and the absence of sufficient numbers of homologs in viral databases. Here, we describe the isolation from human feces of a novel lytic phage with siphovirus morphology, φPDS1, infecting Parabacteroides distasonis APCS2/PD, and classified within a newly proposed Sagittacolavirus genus. In silico and biological characterization of this phage is presented in this study. Key to the isolation of φPDS1 was the antibiotic-driven selective enrichment of the bacterial host in a fecal fermenter. Despite producing plaques and lacking genes associated with lysogeny, φPDS1 demonstrates the ability to coexist in liquid culture for multiple days without affecting the abundance of its host. Multiple studies have shown that changes in Parabacteroides distasonis abundance can be linked to various disease states, rendering this novel phage-host pair and their interactions of particular interest.

Influence of age, socioeconomic status, and location on the infant gut resistome across populations.

Antibiotic resistance is a growing global concern, with many ecological niches showing a high abundance of antibiotic resistance genes (ARGs), including the human gut. With increasing indications of ARGs in infants, this study aims to investigate the gut resistome profile during early life at a wider geographic level. To achieve this objective, we utilized stool samples data from 26 studies involving subjects aged up to 3 years from different geographical locations. The 32,277 Metagenome Assembled Genomes (MAGs) previously generated from shotgun sequencing reads from these studies were used for resistome analysis using RGI with the CARD database. This analysis showed that the distribution of ARGs across the countries in our study differed in alpha diversity and compositionally. In particular, the abundance of ARGs was found to vary by socioeconomic status and healthcare access and quality (HAQ) index. Surprisingly, countries having lower socioeconomic status and HAQ indices showed lower ARG abundance, which was contradictory to previous reports. Gram-negative genera, including Escherichia, Enterobacter, Citrobacter, and Klebsiella harbored a particularly rich set of ARGs, which included antibiotics that belong to the Reserve, Access or Watch category, such as glycopeptides, fluoroquinolones, sulfonamides, macrolides, and tetracyclines. We showed that ARG abundance exponentially decreased with time during the first 3 years of life. Many highly ARG-abundant species including Escherichia, Klebsiella, Citrobacter species that we observed are well-known pathobionts found in the infant gut in early life. High abundance of these species and a diverse range of ARGs in their genomes point toward the infant gut, acting as an ARG reservoir. This is a concern and further studies are needed to examine the causal effect and its consequences on long-term health.

Alleviative effects of exopolysaccharides from Limosilactobacillus mucosae CCFM1273 against ulcerative colitis via modulation of gut microbiota and inhibition of Fas/Fasl and TLR4/NF-κB pathways.

Ulcerative colitis (UC) has become a public health challenge as its global prevalence increases annually. The use of prebiotics in healthcare has grown in recent years. Thus, the present study was designed to explore the alleviating effects and mechanisms of exopolysaccharides (EPS) produced by Limosilactobacillus mucosae CCFM1273 on UC. The results indicated that CCFM1273 EPS mitigated the disease symptoms and colonic pathologic damage in DSS-induced colitis mice. Moreover, CCFM1273 EPS improved the intestinal barrier by restoring goblet cell numbers and MUC2 production, enhancing intercellular junctions, and inhibiting epithelial cell apoptosis. In addition, CCFM1273 EPS inhibited colonic inflammation and oxidative stress. Importantly, CCFM1273 EPS augmented short-chain fatty acid (SCFA) producers, leading to increased levels of SCFAs (especially propionic acid), which inhibited the Fas/Fasl pathway and consequently inhibited epithelial apoptosis, and diminished Gram-negative bacteria, further decreasing lipopolysaccharides (LPS), which suppressed the TLR4/NF-κB pathway and consequently suppressed colonic inflammation, eventually relieving UC in mice. This study provides theoretical support for the use of prebiotics in clinical practice for UC.

Dynamic nature of viral and bacterial communities in human faeces.

Bacteriophages are a major component of the gut microbiome and are believed to play a role in establishment and stabilization of microbial communities by influencing taxonomic and functional diversity. We show that the activity of lytic and temperate phages can also significantly affect bacterial community structure in a model of extended colonic retention. Intact fresh human feces were incubated anaerobically at 37°C without homogenization and subjected to metagenomic sequencing. We observed subject-specific blooms and collapses of selected bacteriophage and bacterial populations within some individuals. Most notable were striking collapses of Prevotella populations accompanied by increases in specific bacteriophages. In a number of cases, we even observed a shift from one bacterial "enterotype" to another within 48 h. These results confirm that intact feces represents a highly dynamic ecological system and suggests that colonic retention time could have a profound effect on microbiome composition, including a significant impact by bacteriophages.