It is widely known that faster-growing bacterial cells are more susceptible to many antibiotics. Given this notion, it appears intuitive that antibiotic treatment would enrich slower-growing cells in a clonal population or slower-growing populations in a microbial community, which has been commonly observed. However, experimental observations also show the enrichment of faster-growing subpopulations under certain conditions. Does this apparent discrepancy suggest the uniqueness about different growth environments or the role of additional confounding factors? If so, what could be the major determinant in antibiotic-mediated community restructuring? Combining modeling and quantitative measurements using a barcoded heterogeneous E. coli library, we show that the outcome of antibiotic-mediated community restructuring can be driven by two major factors. One is the variability among the clonal responses of different subpopulations to the antibiotic; the other is their interactions. Our results suggest the importance of quantitative measurements of antibiotic responses in individual clones in predicting community responses to antibiotics and addressing subpopulation interactions.

In the current era, malnutrition is seen as both undernutrition and overweight and obesity; both conditions are caused by nutrient deficiency or excess and improper use or imbalance in the intake of macro and micronutrients. Recent evidence suggests that malnutrition alters the intestinal microbiota, known as dysbiosis. Secretory immunoglobulin A (sIgA) plays an important role in maintaining and increasing beneficial intestinal microbiota populations and protecting against pathogenic species. Depletion of beneficial bacterial populations throughout life is also conditioned by malnutrition. This review aims to synthesize the evidence that establishes an interrelationship between diet, malnutrition, changes in the intestinal flora, and sIgA levels. Targeted nutritional therapies combined with prebiotic, probiotic, and postbiotic administration can restore the immune response in the intestine and the host's homeostasis.

Recurrent cystitis, particularly common in women, substantially diminishes patient quality of life and represents a major clinical practice and public health burden. Increasing development of resistance to antibiotics has encouraged the search for alternative treatments. The benefits of a food supplement associating two Lactobacillus strains with proanthocyanidin A-rich cranberry and cinnamon extracts were evaluated in 80 women with a history of cystitis recurrence.

Post-inclusion recurrence frequency was compared between women taking the investigated supplement daily for 6 months and non-supplemented women, based on patient-completed Acute Cystitis Symptom Score (ACSS) questionnaires.

Two-thirds (64.9%) of supplemented women experienced no further episodes of cystitis during the first 6 months of the study compared to only one-third (31.6%) of non-supplemented women (p=0.004), the difference between the two groups being significant from 3 months onward. ACSS scores revealed significantly fewer and less severe urinary symptoms in supplemented women, as well as a significantly reduced impact of these symptoms on quality of life (p<0.0001).

The results shown by extensive data on women suffering from recurrent cystitis, collected over 8 months, indicate that taking the tested supplement daily for 6 months can provide significant benefits in terms of recurrence frequency, symptoms, and quality of life. The study is registered on the ClinicalTrials.gov site under the identifier NCT04987164.

Antibiotic use has undesirable side-effects on the host, including perturbations of gut microbiota, immunity, and health. Mammalian studies have demonstrated that concomitant/post antibiotic use of pro-, pre-, and synbiotics could re-establish gut microbiota and prevent detrimental host effects. However, studies evaluating similar effects in fish are scanty. This study evaluated the effects of dietary supplementation with a synbiotic mixture on the post-smolt Atlantic salmon gut microbiota, growth performance, and health during antibiotic treatment and subsequent recovery. Fish in five tanks each were fed either a commercial control diet or a synbiotic diet containing Pediococcus acidilactici and fructo-oligosaccharides, for 6 weeks (S1). Then, fish in three tanks per treatment were fed with medicated diets, containing 3500 ppm florfenicol coated onto the control or synbiotic diets, for 2 weeks (S2) and refed with the respective nonmedicated diets for another 3 (S3) and 5 (S4) weeks of recovery period. The fish not subjected to medication were fed the control or synbiotic diets throughout the experimental period. Samples were collected at S1-S4 from both the nonmedicated and medicated fish.

Florfenicol decreased the feed intake in control group. It reduced the growth rate in both control and synbiotic groups with lesser reduction in synbiotic group. Florfenicol did not significantly affect observed taxa and Shannon indexes. Bacterial composition before and after medication clustered distinctly in control and clustered together in synbiotic groups. Lactobacillus dominated in control while Lactobacillus and Pediococcus dominated in synbiotic group during medication and recovery. Florfenicol did not significantly influence the immune or stress response marker gene expressions, though the expression patterns differed between diet groups. Florfenicol did not cause inflammation in the distal intestine or change hepatosomatic index.

This study highlighted the negative impact of a two-week florfenicol treatment on feed intake and growth performance in Atlantic salmon, with moderate effects on gut microbiota and gene expression. Concomitant use of a synbiotic diet helped to maintain the gut microbial composition and influenced the performance positively and immune gene expressions differently during medication. This study indicates the importance of nutritional interventions through synbiotic supplementation as a possible strategy for managing Atlantic salmon during antibiotic treatment.

Escherichia coli (E. coli) serves as a critical indicator microorganism for assessing the prevalence and dissemination of antibiotic resistance, notably harboring various antibiotic-resistant genes (ARGs). Among these, the emergence of the bla NDM gene represents a significant threat to public health, especially since carbapenem antibiotics are vital for treating severe infections caused by Gram-negative bacteria. This study aimed to characterize the antibiotic resistance features of bla NDM-5-positive E. coli strains isolated from waterfowl in several regions of China and elucidate the dissemination patterns of the bla NDM-5 gene. We successfully isolated 103 bla NDM-5-positive E. coli strains from 431 intestinal fecal samples obtained from waterfowl across five provincial-level units in China, with all strains exhibiting multidrug resistance (MDR). Notably, the bla NDM-5 gene was identified on plasmids, which facilitate efficient and stable horizontal gene transfer (HGT). Our adaptability assays indicated that while the bla NDM-5-positive plasmid imposed a fitness cost on the host bacteria, the NDM-5 protein was successfully induced and purified, exhibiting significant enzymatic activity. One strain, designated DY51, exhibited a minimum inhibitory concentration (MIC) for imipenem of 4 mg/L, which escalated to 512 mg/L following exposure to increasing imipenem doses. This altered strain demonstrated stable resistance to imipenem alongside improved adaptability, correlating with elevated relative expression levels of the bla NDM-5 and overexpression of efflux pumps. Collectively, this study highlights the horizontal dissemination of the bla NDM-5 plasmid among E. coli strains, confirms the associated fitness costs, and provides insights into the mechanisms underlying the stable increase in antibiotic resistance to imipenem. These findings offer a theoretical framework for understanding the dissemination dynamics of bla NDM-5 in E. coli, which is essential for developing effective strategies to combat carbapenem antibiotic resistance.

Elucidation of the role of gut microbiota in the metabolism of orally administered drugs may improve therapeutic effectiveness and contribute to the development of personalized medicine. In this study, ten different artificial gut microbiota (AGM), obtained by culturing fecal samples in a continuous fermentation system, were challenged for their metabolizing capacity on a panel of six glucocorticoids selected from either prodrugs or drugs. Data from metabolic stability assays highlighted that, while the hydrolysis-mediated conversion of prodrugs to drugs represented only a minor metabolic pathway, significant differences in the stability of parent compounds and in their conversion rates to multiple reductive metabolites were obtained for the selected drugs. In the latter case, a taxonomic composition-dependent ability to convert parent drugs to metabolites was observed. Indeed, the artificial microbial communities dominated by the genus Bacteroides showed the maximal conversion of parent glucocorticoids to several metabolites. Furthermore, the effect of drugs on AGM was also evaluated through shallow shotgun sequencing and flow cytometry-based total bacterial cell count highlighting that these drugs can affect both the taxonomic composition and growth performances of the human gut microbiota.

The Danish National Hospital Medication Register (DHMR), one of the first nationwide in-hospital medication registries in the world, contains detailed information on medication administration and dispensing.

To provide an overview of the information recorded in the DHMR and to highlight its strengths and limitations as a pharmacoepidemiological research tool.

We reviewed the registry´s geographic and clinical specialty coverage and medications recorded according to the main groups of the Anatomical Therapeutic Chemical classification system.

From May 2018 through December 2023, the DHMR recorded data on more than 1.9 million unique patients from all approximately 50 public hospitals and associated hospital outpatient clinics, totaling 105.3 million recordings of hospital medication use. The registry records detailed data on the indication for medication, medication type, pharmaceutical form, dosage, and administration time, collected through electronic medical record systems. Although the data quality has not yet been evaluated in a scientific context, some potential limitations are known. These include regional differences in the data collection and a lack of data from certain clinical specialties. Due to its recent establishment in 2018, the registered number of patients treated may still be limited for some rarely used medications.

The DHMR is an important new resource for research in Denmark. Combined with the Danish National Prescription Registry, which covers all community pharmacies, it offers access to accurate data on medication exposure in the Danish population. Users should be aware of potential issues with lack of information before 2018.

The antibacterial and immunomodulatory activities of bacteriocins make them attractive targets for development as anti-infective drugs. Although the importance of the enteric nervous system (ENS) in the struggle against infections of the intestine has been demonstrated, whether it is involved in bacteriocins anti-infective mechanisms is poorly defined.

Here, we demonstrated that the bacteriocin Microcin J25 (J25) significantly alleviated diarrhea and intestinal inflammation in piglets caused by enterotoxigenic Escherichia coli (ETEC) infection. Mechanistically, macrophage levels were significantly downregulated after J25 treatment, and this was replicated in a mouse model. Omics analysis and validation screening revealed that J25 treatment induced significant changes in the dopaminergic neuron pathway, but little change in microbial structure. The alleviation of inflammation may occur by down-regulating dopamine receptor (DR) D1 and the downstream DAG-PKC pathway, thus inhibiting arachidonic acid decomposition, and the inhibition of macrophages may occur through the up-regulation of DRD5 and the downstream cAMP-PKA pathway, thus inhibiting NF-κB.

Our studies' findings provide insight into the changes and possible roles of the ENS in J25 treatment of ETEC infection, providing a more sophisticated foundational understanding for developing the application potential of J25.

Recent studies in mice have indicated that the gut microbiome can regulate bone tissue strength. However, prior work involved modifications to the gut microbiome in growing animals and it is unclear if the same changes in the microbiome, applied later in life, would change matrix strength. Here we changed the composition of the gut microbiome before and/or after skeletal maturity (16 weeks of age) using oral antibiotics (ampicillin + neomycin). Male and female mice (n = 143 total, n = 12-17/group/sex) were allocated into five study groups: (1) Unaltered, (2) Continuous (dosing 4-24 weeks of age), (3) Delayed (dosing only 16-24 weeks of age), (4) Initial (dosing 4-16 weeks of age, suspended at 16 weeks), and (5) Reconstituted (dosing from 4-16 weeks following by fecal microbiota transplant from Unaltered donors). Animals were euthanized at 24 weeks of age. In males, bone matrix strength in the femur was 25%-35% less than expected by geometry in mice from the Continuous (p = 0.001), Delayed (p = 0.005), and Initial (p = 0.040) groups as compared to Unaltered. Reconstitution of the gut microbiota led to a bone matrix strength similar to Unaltered animals (p = 0.929). In females, microbiome-induced changes in bone matrix strength followed the same trend as males but were not significantly different, demonstrating a sex-dependent response of bone matrix to the gut microbiota. Minor differences in chemical composition of bone matrix were observed with Raman spectroscopy. Our findings indicate that microbiome-induced impairment of bone matrix in males can be initiated and/or reversed after skeletal maturity. The portion of the femoral cortical bone formed after skeletal maturity (16 weeks) was small; suggesting that microbiome-induced changes in bone matrix occurred without osteoblast/osteoclast turnover through a yet unidentified mechanism. These findings provide evidence that the mechanical properties of bone matrix can be altered in the adult skeleton.

The scarcity of the antifungal drug arsenal highlights an urgent need to develop alternative treatments for candidiasis caused by Candida albicans (C. albicans). As pH is closely associated with C. albicans infection, it could be an essential target in a novel approach for designing antifungal therapy. In this study, a novel intelligent antifungal monomer, dodecylmethylaminoethyl methacrylate (DMAEM), with a pH-responsive tertiary amine group and a methacrylate-derived CC double bond group is developed. It is uncovered that the two functional groups of DMAEM contribute to a dual mode of action. Under acidic pH, the tertiary amine of DMAEM protonates into a cationic fungicide, sharing similar structural and functional characteristics with quaternary ammonium salts, which exerts fungicidal activity by targeting the CHK1 two-component system in C. albicans. At neutral pH, the methacrylate-derived CC double bond group contributes to anti-virulence activity by blocking hyphal formation. In addition, it is also identified that DMAEM suppresses filamentation by altering the extracellular vesicles of C. albicans. These findings support that the novel intelligent pH-responsive monomer could be a therapeutic candidate for treating candidiasis.

The microbiome-gut-brain axis is altered by environmental stressors such as heat, diet, and pollutants as well as microbes in the air, water, and soil. These stressors might alter the host's microbiome and symbiotic relationship by modifying the microbial composition or location. Compartmentalized mutualistic microbes promote the beneficial interactions in the host leading to circulating metabolites and hormones such as insulin and leptin that affect inter-organ functions. Inflammation and oxidative stress induced by environmental stressors may alter the composition, distribution, and activities of the microbes in the microbiomes such that the resultant metabolite and hormone changes are no longer beneficial. The microbiome-gut-brain axis and immune adverse changes that may accompany environmental stressors are reviewed for effects on innate and adaptive immune cells, which may make host immunity less responsive to pathogens and more reactive to self-antigens. Cardiovascular and fluid exchanges to organs might adversely alter organ functionality. Organs, especially the brain, need a consistent supply of nutrients and clearance of debris; disruption of these exchanges by stressors, and involvement of gut microbiome are discussed regarding neural dysfunctions with Alzheimer's disease, autistic spectrum disorders, viral infections, and autoimmune diseases. The focus of this review includes the manner in which environmental stressors may disrupt gut microbiota leading to adverse immune and hormonal influences on development of neuropathology related to hyperhomocysteinemia, inflammation, and oxidative stress, and how certain therapeutics may be beneficial. Strategies are explored to lessen detrimental effects of environmental stressors on central and peripheral health navigated toward (1) understanding neurological disorders and (2) promoting environmental and public health and well-being.

The purpose of this study was to investigate the improvement of the intestinal barrier and gut microbiota in mice with antibiotic-associated diarrhea (AAD) using Lactiplantibacillus plantarum ELF051 combined with Astragalus polysaccharides. The amoxicillin, clindamycin, and streptomycin triple-mixed antibiotic-induced AAD models were administered with L. plantarum ELF051 or Astragalus polysaccharides or L. plantarum ELF051 + Astragalus polysaccharides for 14 days. Our findings revealed that the combination of L. plantarum ELF051 and Astragalus polysaccharides elevated the number of goblet cells and enhanced the proportion of mucous within the colon tissue. Furthermore, the expression of sIgA and IgG were upregulated, while the levels of IL-17A, IL-4, DAO, D-LA, LPS, and TGF-β1 were downregulated. L. plantarum ELF051 combined with Astragalus polysaccharides elevated the expression of tight junction (TJ) proteins, facilitating intestinal mucosal repair via Smad signaling nodes. Furthermore, their combination effectively increased the relative abundance of lactic acid bacteria (LAB) and Allobaculum, and decreased the relative abundance of Bacteroides and Blautia. Spearman rank correlation analysis demonstrated that LAB were closely related to permeability factors, immune factors, and indicators of intestinal barrier function. In summary, the effect of combining L. plantarum ELF051 and Astragalus polysaccharides on AAD mice was achieved by enhancing intestinal barrier function and regulating the composition of the gut microbiota.

Bacteria in the genus Staphylococcus are pathogenic and harmful to humans. Alarmingly, some Staphylococcus, such as methicillin-resistant S. aureus (MRSA) and vancomycin-resistant S. aureus (VRSA) have spread worldwide and become notoriously resistant to antibiotics, threatening and concerning public health. Hence, the development of new Staphylococcus-targeting diagnostic and therapeutic agents is urgent. Here, we chose the S. aureus-secreted siderophore staphyloferrin A (SA) as a guiding unit. We developed a series of Staphyloferrin A conjugates (SA conjugates) and showed the specific targeting ability to Staphylococcus bacteria. Furthermore, among the structural factors we evaluated, the stereo-chemistry of the amino acid backbone of SA conjugates is essential to efficiently target Staphylococci. Finally, we demonstrated that fluorescent Staphyloferrin A probes (SA-FL probes) could specifically target Staphylococci in complex bacterial mixtures.

Antimicrobial resistance mediated by extended-spectrum beta-lactamase (ESBL)- and plasmid-mediated cephalosporinase (AmpC)-producing Enterobacterales, as well as carbapenemase-producing Enterobacterales have globally increased among companion animals, posing a potential health risk to humans in contact with them. This prospective longitudinal study investigates the transfer of ESBL/AmpC- and carbapenemase-producing Enterobacterales between companion animals and their cohabitant humans in Portugal (PT) and the United Kingdom (UK) during animal infection. Fecal samples and nasal swabs collected from dogs and cats with urinary tract infection (UTI) or skin and soft tissue infection (SSTI), and their cohabitant humans were screened for resistant strains. Relatedness between animal and human strains was established by whole-genome sequencing (WGS). ESBL/AmpC-producing Enterobacterales were detected in companion animals (PT = 55.8%; UK = 36.4%) and humans (PT = 35.9%; UK = 12.5%). Carbapenemase-producing Enterobacterales carriage was observed in one dog from Portugal (2.6%) and another dog from the UK (4.5%). Transmission of index clinical ESBL-producing Escherichia coli and Klebsiella pneumoniae strains to cohabitant humans was observed in three Portuguese households (6.9%, n = 43), with repeated isolation of the index strains on fecal samples from the animals and their cohabiting humans. In addition, longitudinal sharing of E. coli strains carried by companion animals and their owners was observed in other two Portuguese households and two households from the UK. Furthermore, a multidrug-resistant ACT-24-producing Enterobacter hormaechei subsp. hoffmannii strains were also shared within another Portuguese household. These results highlight the importance of the household as an epidemiological unit in the efforts to mitigate the spread of antimicrobial resistance, further emphasizing the need for antimicrobial surveillance in this context, capable of producing data that can inform and evaluate public health actions.

The human digestive system harbors a vast diversity of commensal bacteria and maintains a symbiotic relationship with them. However, imbalances in the gut microbiota accompany various diseases, such as inflammatory bowel diseases (IBDs) and colorectal cancers (CRCs), which significantly impact the well-being of populations globally. Glycosylation of the mucus layer is a crucial factor that plays a critical role in maintaining the homeostatic environment in the gut. This review delves into how the gut microbiota, immune cells, and gut mucus layer work together to establish a balanced gut environment. Specifically, the role of glycosylation in regulating immune cell responses and mucus metabolism in this process is examined.

Urogenital schistosomiasis caused by Schistosoma haematobium affects approximately 110 million people globally, with the majority of cases in low- and middle-income countries. Schistosome infections have been shown to impact the host immune system, gene expression, and microbiome composition. Studies have demonstrated variations in pathology between schistosome subspecies. In the case of S. haematobium, infection has been associated with HIV acquisition and bladder cancer. However, the underlying pathophysiology has been understudied compared to other schistosome species. This systematic review comprehensively investigates and assimilates the effects of S. haematobium infection on systemic and local host mucosal immunity, cellular gene expression and microbiome.

We conducted a systematic review assessing the reported effects of S. haematobium infections and anthelmintic treatment on the immune system, gene expression and microbiome in humans and animal models. This review followed PRISMA guidelines and was registered prospectively in PROSPERO (CRD42022372607). Randomized clinical trials, cohort, cross-sectional, case-control, experimental ex vivo, and animal studies were included. Two reviewers performed screening independently.

We screened 3,177 studies and included 94. S. haematobium was reported to lead to: (i) a mixed immune response with a predominant type 2 immune phenotype, increased T and B regulatory cells, and select pro-inflammatory cytokines; (ii) distinct molecular alterations that would compromise epithelial integrity, such as increased metalloproteinase expression, and promote immunological changes and cellular transformation, specifically upregulation of genes p53 and Bcl-2; and (iii) microbiome dysbiosis in the urinary, intestinal, and genital tracts.

S. haematobium induces distinct alterations in the host's immune system, molecular profile, and microbiome. This leads to a diverse range of inflammatory and anti-inflammatory responses and impaired integrity of the local mucosal epithelial barrier, elevating the risks of secondary infections. Further, S. haematobium promotes cellular transformation with oncogenic potential and disrupts the microbiome, further influencing the immune system and genetic makeup. Understanding the pathophysiology of these interactions can improve outcomes for the sequelae of this devastating parasitic infection.

Staphylococcus aureus is a common cause of diverse infections, ranging from superficial to invasive, affecting both humans and animals. The widespread use of antibiotics in clinical treatments has led to the emergence of antibiotic-resistant strains and small colony variants. This surge presents a significant challenge in eliminating infections and undermines the efficacy of available treatments. The bacterial Save Our Souls (SOS) response, triggered by genotoxic stressors, encompasses host immune defenses and antibiotics, playing a crucial role in bacterial survival, invasiveness, virulence, and drug resistance. Accumulating evidence underscores the pivotal role of the SOS response system in the pathogenicity of S. aureus. Inhibiting this system offers a promising approach for effective bactericidal treatments and curbing the evolution of antimicrobial resistance. Here, we provide a comprehensive review of the activation, impact, and key proteins associated with the SOS response in S. aureus. Additionally, perspectives on therapeutic strategies targeting the SOS response for S. aureus, both individually and in combination with traditional antibiotics are proposed.

To study the clinical, radiographic and microbiological outcomes after surgical treatment of peri-implantitis, with or without adjunctive systemic antibiotics.

Eighty-four patients (113 implants) with peri-implantitis were randomized into three groups (A, amoxicillin and metronidazole; B, phenoxymethylpenicillin and metronidazole; or C, placebo). Treatment included resective surgery and implant surface decontamination with adjunctive antibiotics or placebo. Primary outcomes were probing pocket depth (PPD) reduction and marginal bone level (MBL) stability. Secondary outcomes were treatment success (defined as PPD ≤ 5 mm, bleeding on probing [BOP] ≤ 1site, absence of suppuration on probing [SOP] and absence of progressive bone loss of >0.5 mm), changes in BOP/SOP, mucosal recession (REC), clinical attachment level (CAL), bacterial levels and adverse events. Outcomes were evaluated for up to 12 months. The impact of potential prognostic indicators on treatment success was evaluated using multilevel logistic regression analysis.

A total of 76 patients (104 implants) completed the study. All groups showed clinical and radiological improvements over time. Statistically significant differences were observed between groups for MBL stability (A = 97%, B = 89%, C = 76%), treatment success (A = 68%, B = 66%, C = 28%) and bacterial levels of Aggregatibacter actinomycetemcomitans and Tannerella forsythia, favouring antibiotics compared to placebo. Multiple regression identified antibiotic use as potential prognostic indicator for treatment success. Gastrointestinal disorders were the most reported adverse events in the antibiotic groups.

Adjunctive systemic antibiotics resulted in additional improvements in MBL stability. However, the potential clinical benefits of antibiotics need to be carefully balanced against the risk of adverse events and possible antibiotic resistance.

Some herbal extracts contain relatively high amounts of lipopolysaccharide (LPS). Because orally administered LPS activates innate immunity without inducing inflammation, it plays a role as an active ingredient in herbal extracts. However, the LPS content in herbal extracts remains extensively unevaluated. This study aimed to create a database of LPS content in herbal extracts; therefore, the LPS content of 414 herbal extracts was measured and the macrophage activation potential was evaluated. The LPS content of these hot water extracts was determined using the kinetic-turbidimetric method. The LPS concentration ranged from a few ng/g to hundreds of μg/g (Standard Escherichia coli LPS equivalent). Twelve samples had a high-LPS-content of > 100 μg/g, including seven samples from roots and three samples from leaves of the herbal extracts. These samples showed high phagocytosis and NO production capacity, and further investigation using polymyxin B, an LPS inhibitor, significantly inhibited macrophage activation. This study suggests that some herbal extracts contain sufficient LPS concentration to activate innate immunity. Therefore, a new approach to evaluate the efficacy of herbal extracts based on their LPS content was proposed. A database listing the LPS content of different herbal extracts is essential for this approach.

Legumes are widely appreciated for their abundant reserves of insoluble dietary fiber, which are characterized by their high fiber content and diverse bioactive compounds. Insoluble dietary fiber in leguminous crops is primarily localized in the structural cell walls and outer integument and exhibits strong hydrophilic properties that enable water absorption and volumetric expansion, resulting in increased food bulk and viscosity. This contributes to enhanced satiety and accelerated gastrointestinal transit. The benefits of legume insoluble dietary fiber extend to its notable antioxidant, anti-inflammatory, and anti-cancer properties, as well as its ability to modulate the composition of the intestinal microbiota, promoting the growth of beneficial bacteria while suppressing the proliferation of harmful pathogens, thereby promoting optimal intestinal health. It is highly valued as a valuable thickening agent, stabilizer, and emulsifier, contributing to the texture and stability of a wide range of food products.

IgA nephropathy, presently recognized as the foremost primary glomerular disorder, emerges as a principal contributor to renal failure globally, with its pathogenesis yet to be fully elucidated. Extensive research has highlighted the critical role of gut microbiome in the onset and progression of IgA nephropathy, underscoring its importance in accurately delineating the disease's etiology. For example, gut microbiome dysbacteriosis can lead to the production of nephritogenic IgA1 antibodies, which form immune complexes that deposit in the kidneys, causing inflammation and damage. The gut microbiome, a source of numerous bioactive compounds, interacts with the host and plays a regulatory role in gut-immune axis modulation, earning it the moniker of the "second brain." Recent investigations have particularly emphasized a significant correlation between IgA nephropathy and gut microbiome dysbacteriosis. This article offers a detailed overview of the pathogenic mechanisms of IgA nephropathy, specifically focusing on elucidating how alterations in the gut microbiome are associated with anomalies in the intestinal mucosal system in IgA nephropathy. Additionally, it describes the possible influence of gut microbiome on recurrent IgA nephropathy following kidney transplantation. Furthermore, it compiles potential therapeutic interventions, offering both theoretical and practical foundations for the management of IgA nephropathy. Lastly, the challenges currently faced in the therapeutic approaches to IgA nephropathy are discussed.

Trimethylamine N-oxide (TMAO), a metabolite produced by intestinal microbiota through metabolizing phosphatidylcholine, choline, l-carnitine and betaine in the diet, has been implicated in the pathogenesis of atherosclerosis (AS). Concurrently, dietary polyphenols have garnered attention for their potential to ameliorate obesity, diabetes and atherosclerosis primarily by modulating the intestinal microbial structure. Hickory (Carya cathayensis) nut, a polyphenol-rich food product favored for its palatability, emerges as a candidate for exploration.

The relationship between polyphenol of hickory nut and atherosclerosis prevention will be firstly clarified, providing theoretical basis for the discovery of natural products counteracting TMAO-induced AS process in hickory nut.

Employing Enzyme-linked Immunosorbent Assay (ELISA) and histological examination of aortic samples, the effects of total polyphenol extract on obesity index, inflammatory index and pathological changes of atherosclerosis in C57BL/6 J mice fed with high-fat and high choline diet were evaluated. Further, the composition, abundance, and function of mouse gut microbiota were analyzed through 16srDNA sequencing. Concurrently, the levels of TMAO and the expression of key enzymes (CutC and FMO3) involved in its synthesis are quantified using ELISA, Western Blot and Real-Time Quantitative PCR (RT-qPCR). Additionally, targeted metabolomic profiling of the hickory nut polyphenol extract was conducted, accompanied by molecular docking simulations to predict interactions between candidate polyphenols and the CutC/FMO3 using Autodock Vina. Finally, the docking prediction were verified by microscale thermophoresis (MST) .

Polyphenol extracts of hickory nut improved the index of obesity and inflammation, and alleviated the pathological changes of atherosclerosis in C57BL/6 J mice fed with high-fat and high-choline diet. Meanwhile, these polyphenol extracts also changed the composition and function of intestinal microbiota, and increased the abundance of microorganisms in mice. Notably, the abundance of intestinal microbiota endowed with CutC gene was significantly reduced, coherent with expression of CutC catalyzing TMA production. Moreover, polyphenol extracts also decreased the expression of FMO3 in the liver, contributing to the reduction of TMAO levels in serum. Furthermore, metabonomic profile analysis of these polyphenol extracts identified 647 kinds of polyphenols. Molecular docking predication further demonstrated that Casuariin and Cinnamtannin B2 had the most potential inhibition on the enzymatic activities of CutC or FMO3, respectively. Notably, MST analysis corroborated the potential for direct interaction between CutC enzyme and available polyphenols such as Corilagin, (-)-Gallocatechin gallate and Epigallocatechin gallate.

Hickory polyphenol extract can mitigate HFD-induced AS by regulating intestinal microflora in murine models. In addition, TMA-FMO3-TMAO pathway may play a key role in this process. This research unveils, for the inaugural time, the complex interaction between hickory nut-derived polyphenols and gut microbial, providing novel insights into the role of dietary polyphenols in AS prevention.

To address antimicrobial resistance, antimicrobial stewardship (AMS) principles must be implemented and adhered to. Clinical decision aids such as the MicroGuideTM app are an important part of these efforts. We sought to evaluate the consistency of core AMS information and the diversity of classification thresholds for healthcare-associated pneumonia (HAP) in the MicroGuide app.

Guidelines in the MicroGuide app were extracted and analysed for content related to AMS and HAP. Guidelines were characterized according to HAP naming classification; community-acquired pneumonia (CAP) classifications were analysed to serve as a comparator group.

In total, 115 trusts (119 hospitals) were included. Nearly all hospitals had developed MicroGuide sections on AMS (n = 112/119, 94%) and sepsis management (n = 117/119, 98%). Other AMS sections were outpatient parenteral antimicrobial therapy (47%), antifungal stewardship (70%), critical care (23%) and IV to oral switch therapy (83%). Only 9% of hospitals included guidance on the maximum six key AMS sections identified. HAP definitions varied widely across hospitals with some classifying by time to onset and some classifying by severity or complexity. The largest proportion of HAP guidelines based classification on severity/complexity (n = 69/119, 58%). By contrast, definitions in CAP guidelines were uniform.

The high heterogeneity in HAP classification identified suggests inconsistency of practice in identifying thresholds for HAP in the UK. This complicates HAP management and AMS practices. To address HAP in alignment with AMS principles, a comprehensive strategy that prioritizes uniform clinical definitions and thresholds should be developed.

Diabetes mellitus is a chronic disease affecting glucose metabolism. The pathophysiological reactions underpinning the disease can lead to the development of late diabetes complications. The gut microbiota plays important roles in weight regulation and the maintenance of a healthy digestive system. Obesity, diabetes mellitus, diabetic retinopathy, diabetic nephropathy and diabetic neuropathy are all associated with a microbial imbalance in the gut. Modern technical equipment and advanced diagnostic procedures, including xmolecular methods, are commonly used to detect both quantitative and qualitative changes in the gut microbiota. This review summarises collective knowledge on the role of the gut microbiota in both types of diabetes mellitus and their late complications, with a particular focus on diabetic foot syndrome.

The Human Microbiome Project, Earth Microbiome Project, and next-generation sequencing have advanced novel genome association, host genetic linkages, and pathogen identification. The microbiome is the sum of the microbes, their genetic information, and their ecological niche. This study will describe how millions of bacteria in the gut affect the human body in health and disease. The gut microbiome changes in relation with age, with an increase in Bacteroidetes and Firmicutes. Host and environmental factors affecting the gut microbiome are diet, drugs, age, smoking, exercise, and host genetics. In addition, changes in the gut microbiome may affect the local gut immune system and systemic immune system. In this study, we discuss how the microbiome may affect the metabolism of healthy subjects or may affect the pathogenesis of metabolism-generating metabolic diseases. Due to the high number of publications on the argument, from a methodologically point of view, we decided to select the best papers published in referred journals in the last 3 years. Then we selected the previously published papers. The major goals of our study were to elucidate which microbiome and by which pathways are related to healthy and disease conditions.

The human gut microbiota (GM), which consists of a complex and diverse ecosystem of bacteria, plays a vital role in overall wellness. However, the delicate balance of this intricate system is being compromised by the widespread presence of environmental toxins. The intricate connection between contaminants in the environment and human well-being has garnered significant attention in recent times. Although many environmental pollutants and their toxicity have been identified and studied in laboratory settings and animal models, there is insufficient data concerning their relevance to human physiology. Consequently, research on the toxicity of environmental toxins in GM has gained prominence in recent years. Various factors, such as air pollution, chemicals, heavy metals, and pesticides, have a detrimental impact on the composition and functioning of the GM. This comprehensive review aims to comprehend the toxic effects of numerous environmental pollutants, including antibiotics, endocrine-disrupting chemicals, heavy metals, and pesticides, on GM by examining recent research findings. The current analysis concludes that different types of environmental toxins can lead to GM dysbiosis and have various potential adverse effects on the well-being of animals. We investigate the alterations to the GM composition induced by contaminants and their impact on overall well-being, providing a fresh perspective on research related to pollutant exposure.

Infectious diseases have long posed a significant threat to global health and require constant innovation in treatment approaches. However, recent groundbreaking research has shed light on a previously overlooked player in the pathogenesis of disease-the human microbiome. This review article addresses the intricate relationship between the microbiome and infectious diseases and unravels its role as a crucial mediator of host-pathogen interactions. We explore the remarkable potential of harnessing this dynamic ecosystem to develop innovative treatment strategies that could revolutionize the management of infectious diseases. By exploring the latest advances and emerging trends, this review aims to provide a new perspective on combating infectious diseases by targeting the microbiome.

Nonalcoholic fatty liver disease, recently re-named metabolic dysfunction-associated steatotic fatty liver disease, is considered the most prevalent liver disease worldwide. Its molecular initiation events are multiple and not always well-defined, comprising insulin resistance, chronic low-grade inflammation, gut dysbiosis, and mitochondrial dysfunction, all of them acting on genetic and epigenetic grounds. Nowadays, there is a growing public health threat, which is antibiotic excessive use and misuse. This widespread use of antibiotics not only in humans, but also in animals has led to the presence of residues in derived foods, such as milk and dairy products. Furthermore, antibiotics have been used for many decades to control certain bacterial diseases in high-value fruit and vegetables. Recently, it has been emphasised that antibiotic-induced changes in microbial composition reduce microbial diversity and alter the functional attributes of the microbiota. These antibiotic residues impact human gut flora, setting in motion a chain of events that leads straight to various metabolic alterations that can ultimately contribute to the onset and progression of NAFLD.

The aim of this study was to compare the effects of feeding pasteurized waste milk or saleable milk to calves on weight, health and emergence of antimicrobial resistance in Escherichia coli strains isolated from those calves. An experimental study under field conditions on a commercial pasture-based Argentinian dairy farm was carried out. Forty Holstein calves were assigned randomly to either pasteurized waste milk (PWM) or non-pasteurized saleable milk (SM). The antimicrobial agents (AM) used on the farm, both to treat or prevent diseases, were recorded. The passive immunity level, calf live weight, AM presence in milk, clinical examination of calves, and E. coli isolation and identification, were performed. A total of 258 E. coli strains were isolated from fecal samples (132 isolates from SM calves and 126 from PWM calves at six sampling times). All E. coli isolated were used to perform AM susceptibility tests (disc diffusion and agar dilution). No differences were observed between groups in health parameters, average daily gain or prevalence of resistant E. coli strains to any AM evaluated throughout the study. Peaks of trimethoprim, sulfamethoxazole and enrofloxacin minimum inhibitory concentration (MIC) were observed at 30 d in E. coli from both groups of calves, whilst additional peaks to tetracyclin and ampicillin were observed only in SM calves. All MIC apart from gentamicin decreased at 75 and 90 d of age (during the weaning period). Gentamicin MIC behaved differently, having no peaks and increasing at 90 d only in PWM group. In conclusion, we found no evidence that emergence of antibiotic resistance is related to the consumption of pasteurized waste milk.

Although the spread of antimicrobial resistance (AMR) through food and its production poses a significant concern, there is limited research on the prevalence of AMR bacteria in various agri-food products. Sequencing technologies are increasingly being used to track the spread of AMR genes (ARGs) in bacteria, and metagenomics has the potential to bypass some of the limitations of single isolate characterization by allowing simultaneous analysis of the agri-food product microbiome and associated resistome. However, metagenomics may still be hindered by methodological biases, presence of eukaryotic DNA, and difficulties in detecting low abundance targets within an attainable sequence coverage. The goal of this study was to assess whether limits of detection of ARGs in agri-food metagenomes were influenced by sample type and bioinformatic approaches.

We simulated metagenomes containing different proportions of AMR pathogens and analysed them for taxonomic composition and ARGs using several common bioinformatic tools. Kraken2/Bracken estimates of species abundance were closest to expected values. However, analysis by both Kraken2/Bracken indicated presence of organisms not included in the synthetic metagenomes. Metaphlan3/Metaphlan4 analysis of community composition was more specific but with lower sensitivity than the Kraken2/Bracken analysis. Accurate detection of ARGs dropped drastically below 5X isolate genome coverage. However, it was sometimes possible to detect ARGs and closely related alleles at lower coverage levels if using a lower ARG-target coverage cutoff (< 80%). While KMA and CARD-RGI only predicted presence of expected ARG-targets or closely related gene-alleles, SRST2 (which allows read to map to multiple targets) falsely reported presence of distantly related ARGs at all isolate genome coverage levels. The presence of background microbiota in metagenomes influenced the accuracy of ARG detection by KMA, resulting in mcr-1 detection at 0.1X isolate coverage in the lettuce but not in the beef metagenome.

This study demonstrates accurate detection of ARGs in synthetic metagenomes using various bioinformatic methods, provided that reads from the ARG-encoding organism exceed approximately 5X isolate coverage (i.e. 0.4% of a 40 million read metagenome). While lowering thresholds for target gene detection improved sensitivity, this led to the identification of alternative ARG-alleles, potentially confounding the identification of critical ARGs in the resistome. Further advancements in sequencing technologies providing increased coverage depth or extended read lengths may improve ARG detection in agri-food metagenomic samples, enabling use of this approach for tracking clinically important ARGs in agri-food samples.

Recent studies in mice have indicated that the gut microbiome can regulate bone tissue strength. However, prior work involved modifications to the gut microbiome in growing animals and it is unclear if the same changes in the microbiome, applied later in life, would change matrix strength. Here we changed the composition of the gut microbiome before and/or after skeletal maturity (16 weeks of age) using oral antibiotics (ampicillin + neomycin). Male and female mice (n=143 total, n=12-17/group/sex) were allocated into five study groups:1) Unaltered, 2) Continuous (dosing 4-24 weeks of age), 3) Delayed (dosing only 16-24 weeks of age), 4) Initial (dosing 4-16 weeks of age, suspended at 16 weeks), and 5) Reconstituted (dosing from 4-16 weeks following by fecal microbiota transplant from Unaltered donors). Animals were euthanized at 24 weeks of age. In males, bone matrix strength in the femur was 25-35% less than expected from geometry in mice from the Continuous (p= 0.001), Delayed (p= 0.005), and Initial (p=0.040) groups as compared to Unaltered. Reconstitution of the gut microbiota, however, led to a bone matrix strength similar to Unaltered animals (p=0.929). In females, microbiome-induced changes in bone matrix strength followed the same trend as males but were not significantly different, demonstrating sex-related differences in the response of bone matrix to the gut microbiota. Minor differences in chemical composition of bone matrix were observed (Raman spectroscopy). Our findings indicate that microbiome-induced impairment of bone matrix in males can be initiated and/or reversed after skeletal maturity. The portion of the femoral cortical bone formed after skeletal maturity (16 weeks) is small; however, this suggests that microbiome-induced changes in bone matrix occur without osteoblast/osteoclast turnover using an, as of yet unidentified mechanism. These findings add to evidence that the mechanical properties of bone matrix can be altered in the adult skeleton.

Despite their crucial importance for human health, there is still relatively limited knowledge on how the gut resistome changes or responds to antibiotic treatment across ages, especially in the latter case. Here, we use fecal metagenomic data from 662 Danish infants and 217 young adults to fill this gap. The gut resistomes are characterized by a bimodal distribution driven by E. coli composition. The typical profile of the gut resistome differs significantly between adults and infants, with the latter distinguished by higher gene and plasmid abundances. However, the predominant antibiotic resistance genes (ARGs) are the same. Antibiotic treatment reduces bacterial diversity and increased ARG and plasmid abundances in both cohorts, especially core ARGs. The effects of antibiotic treatments on the gut microbiome last longer in adults than in infants, and different antibiotics are associated with distinct impacts. Overall, this study broadens our current understanding of gut resistome dynamics and the impact of antibiotic treatment across age groups.

SUMMARYOver the past decade, hundreds of studies have characterized the microbial communities found in human-associated built environments (BEs). These have focused primarily on how the design and use of our built spaces have shaped human-microbe interactions and how the differential selection of certain taxa or genetic traits has influenced health outcomes. It is now known that the more removed humans are from the natural environment, the greater the risk for the development of autoimmune and allergic diseases, and that indoor spaces can be harsh, selective environments that can increase the emergence of antimicrobial-resistant and virulent phenotypes in surface-bound communities. However, despite the abundance of research that now points to the importance of BEs in determining human-microbe interactions, only a fraction of non-human animal structures have been comparatively explored. It is here, in the context of human-associated BE research, that we consider the microbial ecology of animal-built natural nests and burrows, as well as artificial enclosures, and point to areas of primary interest for future research.

Lipopolysaccharide (LPS) can traverse the intestinal barrier and enter bloodstream, causing endotoxemia and triggering inflammation. Increased circulating LPS was reported in arterial thromboembolism. We investigated whether increased LPS levels occur in acute pulmonary embolism (PE) and if it is associated with a prothrombotic state.

We studied 120 normotensive PE patients (aged 59 [48-68] years) on admission, after 5-7 days, and after a 3-month anticoagulation. Serum LPS levels, along with zonulin, a marker of gut permeability, endogenous thrombin potential (ETP), fibrin clot permeability (Ks), clot lysis time (CLT), fibrinolysis proteins, and platelet markers were assessed.

Median LPS concentration on admission was 70.5 (61.5-82) pg/mL (min-max, 34-134 pg/mL), in association with C-reactive protein (r = 0.22, p = 0.018), but not with fibrinogen, D-dimer or platelet markers. Patients with more severe PE had higher LPS levels compared with the remainder. Median zonulin level was 3.26 (2.74-4.08) ng/mL and correlated with LPS (r = 0.66, p < 0.0001). Patients with baseline LPS levels in the top quartile (≥82 pg/mL; n = 29) compared to lower quartiles had 18.6 % increased ETP, 14.5 % reduced Ks, and 25.3 % prolonged CLT, related to higher plasminogen activator inhibitor type 1 (PAI-1) levels. LPS decreased by 23.4 % after 5-7 days and by 40.4 % after 3-month anticoagulation together with reduced zonulin by 18.4 % and 22.3 %, respectively, compared to baseline (all p < 0.001). LPS levels were not related with fibrin characteristics and other variables assessed at 3 months.

Low-grade endotoxemia is detectable in patients with acute PE and may contribute to increased thrombin generation and PAI-1-mediated hypofibrinolysis.

Antibiotics have transformed medicine, saving millions of lives since they were first used to treat a bacterial infection. However, antibiotics administered to target a specific pathogen can also cause collateral damage to the patient's resident microbial population. These drugs can suppress the growth of commensal species which provide protection against colonization by foreign pathogens, leading to an increased risk of subsequent infection. At the same time, a patient's microbiota can harbour potential pathogens and, hence, be a source of infection. Antibiotic-induced selection pressure can cause overgrowth of resistant pathogens pre-existing in the patient's microbiota, leading to hard-to-treat superinfections. In this Review, we explore our current understanding of how antibiotic therapy can facilitate subsequent infections due to both loss of colonization resistance and overgrowth of resistant microorganisms, and how these processes are often interlinked. We discuss both well-known and currently overlooked examples of antibiotic-associated infections at various body sites from various pathogens. Finally, we describe ongoing and new strategies to overcome the collateral damage caused by antibiotics and to limit the risk of antibiotic-associated infections.

This meta-analysis examined the effect of macrolides on resolution of community-acquired pneumonia (CAP) and interpretation of clinical benefit according to microbiology; emphasis is given to data under-reported countries (URCs).

This meta-analysis included 47 publications published between 1994 and 2022. Publications were analysed for 30-d mortality (58 759 patients) and resolution of CAP (6465 patients). A separate meta-analysis was done for the prevalence of respiratory pathogens in URCs.

Mortality after 30 d was reduced by the addition of macrolides (odds ratio [OR] 0.65, 95% confidence interval [CI] 0.51-0.82). The OR for CAP resolution when macrolides were added to the treatment regimen was 1.23 (95% CI 1.00-1.52). In the CAP resolution analysis, the most prevalent pathogen was Streptococcus pneumoniae (12.68%; 95% CI 9.36-16.95%). Analysis of the pathogen epidemiology from the URCs included 12 publications. The most prevalent pathogens were S. pneumoniae (24.91%) and Klebsiella pneumoniae (12.90%).

The addition of macrolides to the treatment regimen led to 35% relative decrease of 30-d mortality and to 23% relative increase in resolution of CAP.