Colonic Bacteria Research Articles

Bacteria undergo significant shifts while archaea maintain stability in Pocillopora damicornis under sustained heat stress

Global warming reportedly poses a critical risk to coral reef ecosystems. Bacteria and archaea are crucial components of the coral holobiont. The response of archaea associated with warming is less well understood than that of the bacterial community in corals. Also, there have been few studies on the dynamics of the microbial community in the coral holobiont under long-term heat stress. In order to track the dynamic alternations in the microbial communities within the heat-stressed coral holobiont, three-week heat-stress monitoring was carried out on the coral Pocillopora damicornis. The findings demonstrate that the corals were stressed at 32 °C, and showed a gradual decrease in Symbiodiniaceae density with increasing duration of heat stress. The archaeal community in the coral holobiont remained relatively unaltered by the increasing temperature, whereas the bacterial community was considerably altered. Sustained heat stress exacerbated the dissimilarities among parallel samples of the bacterial community, confirming the Anna Karenina Principle in animal microbiomes. Heat stress leads to more complex and unstable microbial networks, characterized by an increased average degree and decreased modularity, respectively. With the extension of heat stress duration, the relative abundances of the gene (nifH) and genus (Tistlia) associated with nitrogen fixation increased in coral samples, as well as the potential pathogenic bacteria (Flavobacteriales) and opportunistic bacteria (Bacteroides). Hence, our findings suggest that coral hosts might recruit nitrogen-fixing bacteria during the initial stages of suffering heat stress. An environment that is conducive to the colonization and development of opportunistic and pathogenic bacteria when the coral host becomes more susceptible as heat stress duration increases.

Bile salt hydrolase catalyses formation of amine-conjugated bile acids.

Bacteria in the gastrointestinal tract produce amino acid bile acid amidates that can affect host-mediated metabolic processes1-6; however, the bacterial gene(s) responsible for their production remain unknown. Herein, we report that bile salt hydrolase (BSH) possesses dual functions in bile acid metabolism. Specifically, we identified a previously unknown role for BSH as an amine N-acyltransferase that conjugates amines to bile acids, thus forming bacterial bile acid amidates (BBAAs). To characterize this amine N-acyltransferase BSH activity, we used pharmacological inhibition of BSH, heterologous expression of bsh and mutants in Escherichia coli and bsh knockout and complementation in Bacteroides fragilis to demonstrate that BSH generates BBAAs. We further show in a human infant cohort that BBAA production is positively correlated with the colonization of bsh-expressing bacteria. Lastly, we report that in cell culture models, BBAAs activate host ligand-activated transcription factors including the pregnane X receptor and the aryl hydrocarbon receptor. These findings enhance our understanding of how gut bacteria, through the promiscuous actions of BSH, have a significant role in regulating the bile acid metabolic network.

Enhanced osteogenic and antibacterial properties of titanium implant surface modified with Zn-incorporated nanowires: Preclinical invitro and invivo investigations.

This study aimed to synthesize zinc-incorporated nanowires structure modified titanium implant surface (Zn-NW-Ti) and explore its superior osteogenic and antibacterial properties invitro and invivo. Zn-NW-Ti was synthesized via displacement reactions between zinc sulfate solutions and the titanium (Ti) surface, which was pretreated by hydrofluoric acid etching and hyperthermal alkalinization. The physicochemical properties of the Zn-NW-Ti surface were examined. Moreover, the biological effects of Zn-NW-Ti on MC3T3-E1 cells and its antibacterial property against oral pathogenic bacteria (Staphylococcus aureus, Porphyromonas gingivalis, and Actinobacillus actinomycetemcomitans) compared with sandblasted and acid-etched Ti (SLA-Ti) and nanowires modified Ti (NW-Ti) surface were assessed. Zn-NW-Ti and SLA-Ti modified implants were inserted into the anterior extraction socket of the rabbit mandible with or without exposure to the mixed bacterial solution (S. aureus, P. gingivalis, and A. actinomycetemcomitans) to investigate the osteointegration and antibacterial performance via radiographic and histomorphometric analysis. The Zn-NW-Ti surface was successfully prepared. The resultant titanium surface appeared as a nanowires structure with hydrophilicity, from which zinc ions were released in an effective concentration range. The Zn-NW-Ti surface performed better in facilitating the adhesion, proliferation, and differentiation of MC3T3-E1 cells while inhibiting the colonization of bacteria compared with SLA-Ti and NW-Ti surface. The Zn-NW-Ti implant exhibited enhanced osseointegration invivo, which was attributed to increased osteogenic activity and reduced bacterial-induced inflammation compared with the SLA-Ti implant. The Zn-incorporated nanowires structure modified titanium implant surface exhibited improvements in osteogenic and antibacterial properties, which optimized osteointegration in comparison with SLA titanium implant surface.

Uropathogenic distribution and antibiotic resistance patterns according to multidrug-resistant bacteria colonization status in patients with stroke.

Urinary tract infections (UTI) are common in patients with stroke. The colonization of multidrug-resistant organisms (MDR) has recently become a global issue, and infection with MDR is associated with a poorer prognosis. This study aimed to investigate the uropathogenic distribution in stroke patients according to MDR colonization and investigate the infection risk and antibiotic resistance of each uropathogen to help determine initial antibiotic treatment. This study is a retrospective study conducted on patients who underwent inpatient treatment for stroke at Kosin University Gospel Hospital in 2019 to 2021. The participants were classified into Group VRE if vancomycin-resistant Enterococcus (VRE) colonization was confirmed, Group CRE if carbapenem-resistant Enterobacteriaceae (CRE) colonization was confirmed, and Group Negative if no MDR colonization was confirmed. Urine culture was performed if symptomatic UTI was suspected. Uropathogenic distribution, antibiotic resistance patterns were assessed by one-way analysis of variance, independent t-test, and Pearson chi-square test. And the infection risk factors for each uropathogen were assessed by multinomial logistic regression analysis. Six hundred thirty-three participants were enrolled. The mean age of all participants was 69.77 ± 14.91, with 305 males and 328 females, including 344 hemorrhagic strokes and 289 ischemic strokes. No growth in urine culture was the most common finding (n = 281), followed by Escherichia coli (E.coli) (n = 141), and Enterococcus spp. (n = 80). Group Negative had significantly more cases of no growth in urine culture than Group VRE (Odds ratio [OR], 11.698; 95% confidence interval [CI], 3.566-38.375; P < .001) and than Group CRE (OR, 11.381; 95% CI, 2.665-48.611; P < .001). Group VRE had significantly more E.coli (OR, 2.905; 95% CI, 1.505-5.618; P = .001), and more Enterococcus (OR, 4.550; 95% CI, 2.253-9.187; P < .001) than Group Negative. There was no statistical difference in antibiotic resistance according to MDR colonization in E coli, but for Enterococcus spp., Group VRE and CRE showed significantly more resistance to numerous antibiotics than Group Negative. MDR colonization increases the risk of UTI and is associated with greater antibiotic resistance. For appropriate administration of antibiotics in UTI, continuous monitoring of the latest trends in uropathogenic distribution is required, and clinicians should pay more attention to the use of initial empirical antibiotics in patients with MDR colonization.

LOCAL BIOACTIVATION AND EFFICACY OF PALI-2108: A PROMISING PDE4 INHIBITOR PRODRUG FOR ULCERATIVE COLITIS TREATMENT

Abstract Phosphodiesterase-4 (PDE4) is a key enzyme in cAMP hydrolysis and is involved in various inflammatory and fibrotic diseases, such as ulcerative colitis (UC). PDE4 inhibition elevates intracellular cAMP, downregulates inflammatory cytokines (e.g., TNFα), and reduces cell adhesion molecules, thereby preventing local infiltration of inflammatory cells. Several PDE4 inhibitors (e.g., roflumilast and apremilast) are approved for COPD and psoriasis, with others under development for diseases such as idiopathic pulmonary fibrosis (IPF). Phase 2 clinical trials have shown that oral PDE4 inhibitors enhance clinical remission in UC patients, with a 20% placebo-adjusted improvement with low-dose apremilast. However, oral administration and systemic distribution cause central nervous system (CNS) toxicity (e.g., headaches, nausea, vomiting), leading to therapy discontinuation and limiting efficacy. Targeted and better-tolerated oral treatments are needed to fully exploit PDE4 inhibitors in UC. We assessed the efficacy of PALI-2108, an oral and locally bioactivated PDE4 inhibitor prodrug for UC treatment. PALI-2108 incorporates a galactose-derived sugar moiety, making it minimally absorbed until cleaved by the colonic bacterium enzyme β-glucuronidase. In a DSS-induced UC mouse model, PALI-2108 demonstrated that at doses of 21, 4, 0.75 mg/kg BID, and 1.5 mg/kg daily, it reduced the mean disease activity index (DAI) score over time compared to the DSS control group (Fig 1). Additionally, body weight loss over time was attenuated in the 21 and 4 mg/kg BID groups (Fig 2). A tissue distribution study showed colon preference of PALI-2108 with limited plasma levels and a colon/plasma AUC ratio exceeding 200. Additionally, oxazolone colitis induced mice treated with PALI-2108 showed colon-selective bioactivation, with negligible plasma levels compared to duodenal and ileal tissue. In a target engagement study, we used a CETSA Navigate® assay to measure PALI-2108 binding to cAMP-specific 3’, 5’-cyclic PDE4D in OXZ-treated mice. Melt and shift curves showed similar changes, indicating comparable target engagement in colon tissues between PALI-2108 and apremilast. Finally, in a tolerated dose study, we showed no CNS toxicity and emesis over effective doses in dogs. In conclusion, our results demonstrate local bioactivation of a PDE4 inhibitor pro-drug, PALI-2108, and its colon-specific distribution with limited systemic exposure. PALI-2108 has similar target engagement to other PDE4 inhibitors, dose-dependent efficacy in a UC model, and no systemic toxicity. We believe PALI-2108 is a promising novel therapy for UC, with localized bioactivation, expanded therapeutic window, and potent PDE4 inhibitory activity. PALI-2108 is in development for moderate-to-severe UC and is advancing toward regulatory filing for first-in-human studies. PALI-2108 reduced DSS induced mean disease activity index score (DAI) over time compared to control. PALI-2108 attenuated DSS induced body weight loss over time compared to control.

Multi-cohort shotgun metagenomic analysis of oral and gut microbiota overlap in healthy adults

The multitude of barriers between the mouth and colon may eliminate swallowed oral bacteria. Ascertaining the presence of the same bacteria in the mouth and colon is methodologically challenging partly because 16S rRNA gene sequencing – the most commonly used method to characterize the human microbiota – has low confidence in taxonomic assignments deeper than genus for most bacteria. As different species of the same genus can have low-level variation across the same 16S rRNA gene region, shotgun sequencing is needed to identify a true overlap. We analyzed a curated, multi-cohort, shotgun metagenomic database with species-level taxonomy and clade-specific marker genes to fill this knowledge gap. Using 500 paired fecal/oral (4 oral sites) samples from 4 healthy adult cohorts, we found a minute overlap between the two niches. Comparing marker genes between paired oral and fecal samples with species-level overlap, the pattern of overlap in only 7 individuals was consistent with same-strain colonization. These findings argue against ectopic colonization of oral bacteria in the distal gut in healthy adults.

Bacteria colonization in tumor microenvironment creates a favorable niche for immunogenic chemotherapy

The tumor microenvironment (TME) presents differential selective pressure (DSP) that favors the growth of cancer cells, and monovalent therapy is often inadequate in reversing the cancer cell dominance in the TME. In this work, we introduce bacteria as a foreign species to the TME and explore combinatorial treatment strategies to alter DSP for tumor eradication. We show that cancer-selective chemotherapeutic agents and fasting can provide a strong selection pressure against tumor growth in the presence of bacteria. Moreover, we show that an immunogenic drug (oxaliplatin), but not a non-immunogenic one (5-FU), synergizes with the bacteria to activate both the innate and adaptive immunity in the TME, resulting in complete tumor remission and a sustained anti-tumor immunological memory in mice. The combination of oxaliplatin and bacteria greatly enhances the co-stimulatory and antigen-presenting molecules on antigen-presenting cells, which in turn bridge the cytotoxic T cells for cancer-cell killing. Our findings indicate that rational combination of bacterial therapy and immunogenic chemotherapy can promote anticancer immunity against the immunosuppressive TME.

Sodium butyrate administration improves intestinal development of suckling lambs.

This study was conducted to investigate the effects of sodium butyrate (SB) supplementation on growth performance, intestinal barrier functions, and intestinal bacterial communities in sucking lambs. Forty lambs of 7 d old, with an average body weight (BW) of 4.46 ± 0.45kg, were allocated into the control (CON) or SB group, with each group having five replicate pens (n = 5). Lambs were orally administered SB at 1.8mL/kg BW in the SB group or the same volume of saline in the CON group. Treatments were administered from 7 to 35 d of age, when one lamb from each replicate was slaughtered to obtain intestinal tissues and contents. The results showed that supplementation with SB tended to increase the BW (P = 0.079) and the starter intake (P = 0.089) of lambs at 35 d of age. The average daily gain of lambs in the SB group was significantly greater than that in the CON group (P < 0.05). The villus height of jejunum in the SB group was markedly higher (P < 0.05) than that in the CON group. In ileum, lambs in the SB group had lower (P < 0.05) crypt depth and greater (P < 0.05) villus-to-crypt ratio than those in the CON group. Compared with the CON group, the mRNA and protein expressions of Claudin-1 and Occludin were increased (P < 0.05) in the SB group. Supplementation with SB decreased the relative abundances of pathogenic bacteria, including Clostridia_UCG-014 (P = 0.094) and Romboutsia (P < 0.05), which were negatively associated with the intestinal barrier function genes (P < 0.05). The relative abundance of Succiniclasticum (P < 0.05) was higher in the SB group, and it was positively correlated with the ratio of villi height to crypt depth in the jejunum (P < 0.05). Compared with the CON group, the function "Metabolism of Cofactors and Vitamins" was increased in the SB group lambs (P < 0.05). In conclusion, SB orally administration during suckling period could improve the small intestine development and growth performance of lambs by inhibiting the harmful bacteria (Clostridia_UCG-014, Romboutsia) colonization, and enhancing intestinal barrier functions.

In situ MgO nanoparticle-doped Janus electrospun dressing against bacterial invasion and immune imbalance for irregular wound healing.

Owing to the unpredictable size of wounds and irregular edges formed by trauma, nanofibers' highly customizable and adherent in situ deposition can contribute to intervention in the healing process. However, electrospinning is limited by the constraints of conventional polymeric materials despite its potential for anti-inflammatory and antimicrobial properties. Here, inspired by the Janus structure and biochemistry of nanometal ions, we developed an in situ sprayed electrospinning method to overcome bacterial infections and immune imbalances during wound healing. The bilayer fiber scaffold has a hydrophobic outer layer composed of polycaprolactone (PCL) and a hydrophilic inner layer composed of gelatin, poly(L-lactic acid) (PLLA), and magnesium oxide nanoparticles, constituting the PCL/PLLA-gelatin-MgO (PPGM) electrospun scaffold. This electrospun scaffold blocked the colonization and growth of bacteria and remained stable on the wound for continuous anti-inflammatory properties to promote wound healing. Furthermore, PPGM electrospinning modulated collagen deposition and the inflammatory microenvironment in the full-thickness skin model, significantly accelerating vascularization and epithelialization progression. This personalized Janus electrospun scaffold has excellent potential as a new type of wound dressing for first aid and wound healthcare.

Positive effects of dietary honey and aflatoxin B1 on serum enzymes, superoxide dismutase activity, β-glucuronidase enzyme activity, and colonic probiotic bacteria on rats

Dietary honey as a natural product can attenuate the inflammatory process and prevent several diseases. The current research aimed to assess some positive effects of dietary honey and aflatoxin B1 on serum enzymes, superoxide dismutase activity, β-glucuronidase enzyme activity, and colonic probiotic bacteria in rats. Four kinds of honey were coded as NSH, MOH, SIH, and PUH for Nigella sativa, moringa, pumpkin, and Sidr honey, respectively. Aflatoxin B1 (AFB1) was daily administered orally for rats with a dose of 200 μg/kg until 90 days. The rat groups’ body weights at the beginning and end of the experiment ranged from 311.29 g to 327.55 g, and 302.97 g to 342.77 g respectively. Dietary honey decreased the values of some serum enzymes and protected the animals from AFB1 hepatotoxicity compared with the positive group (+). The concentrations of liver superoxide dismutase activity (SOD) among rat groups ranged from 19.55 u ·g in MOH+AFB1 rat group to 27.21 u·g in SIH+AFB1 rat group. Dietary honey was reported to defend the liver against aflatoxins and enhance the gut microflora as β-glucuronidase activity and colonic probiotic bacteria in rats.

Integrated microbiome, metabolome and transcriptome profiling reveals the beneficial effects of fish oil and Bacillus subtilis jzxj-7 on mouse gut ecosystem.

The effects of fish oil (FO) and Bacillus subtilis jzxj-7 (JZXJ-7) on the colonic physiology, bacteria, metabolites, and gene expressions were studied in C57BL/6J mice. Co-administration of FO and JZXJ-7 was more beneficial than individual supplementation, as evidenced by improved growth performance, enhanced colon crypt depth and goblet cell numbers. FO + JZXJ-7 inhibited colonic fibrosis by downregulating fibrosis marker protein expression and upregulating occludin, claudin-2 and claudin-4 gene expressions. FO + JZXJ-7 ameliorated oxidative stress and inflammation by increasing catalase, superoxide dismutase, total anti-oxidation capacity, and reducing colon tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6 levels. Mechanistically, FO + JZXJ-7 modulated the colon micro-ecological environment by enriching Roseburia, Lachnospiraceae NK4B4, Faecalibaculum and Lactococcus and its derived short-chain fatty acids, and activating Ppara and Car1 mediated peroxisome proliferators-activated receptor (PPAR) and phosphatidylinositol 3 kinase/protein kinase B (PI3K/Akt) signaling. Overall, FO + JZXJ-7 may serve as a promising nutraceutical to improve health by boosting the growth of colonic beneficial bacteria, altering metabolic phenotype, and regulating gene expression.

Extraction of Mucin from Rodent Feces and Determination of O-Linked Oligosaccharide Chain Equivalent Derived from Fecal Mucin.

Since the core protein of mucin in the digesta of the stomach and small intestine, which is less affected by bacteria, remains intact, mucin content can be measured by enzyme-linked immunosorbent assay (ELISA). However, the mucin core protein in bacteria-rich colon digesta and feces is partially hydrolyzed by bacterial enzymes and not fully recognized by mucin antibodies, so mucin cannot be accurately quantified by ELISA. This method quantifies the glycan content linked to the mucin core protein and expresses mucin content in the colon digesta and feces as the equivalent of O-linked oligosaccharide chain. Although mucin glycans are also hydrolyzed by colonic bacteria, this method is a more accurate and simple way to measure mucin content in the digesta of the large intestine and feces than the ELISA method.

Regulation of Aerobic Succinate Transporter dctA of E. coli by cAMP-CRP, DcuS-DcuR, and EIIAGlc: Succinate as a Carbon Substrate and Signaling Molecule

Introduction: C4-dicarboxylates (C4-DC) have emerged as significant growth substrates and signaling molecules for various Enterobacteriaceae during their colonization of mammalian hosts. Particularly noteworthy is the essential role of fumarate respiration during colonization of pathogenic bacteria. To investigate the regulation of aerobic C4-DC metabolism, the study explored the transcriptional control of the main aerobic C4-DC transporter, dctA, under different carbohydrate conditions. In addition, mutants related to carbon catabolite repression (CCR) and C4-DC regulation (DcuS-DcuR) were examined to better understand the regulatory integration of aerobic C4-DC metabolism into CCR. For initial insight into posttranslational regulation, the interaction between the aerobic C4-DC transporter DctA and EIIAGlc from the glucose-specific phosphotransferase system was investigated. Methods: The expression of dctA was characterized in the presence of various carbohydrates and regulatory mutants affecting CCR. This was accomplished by fusing the dctA promoter (PdctA) to the lacZ reporter gene. Additionally, the interaction between DctA and EIIAGlc of the glucose-specific phosphotransferase system was examined in vivo using a bacterial two-hybrid system. Results: The dctA promoter region contains a class I cAMP-CRP-binding site at position −81.5 and a DcuR-binding site at position −105.5. DcuR, the response regulator of the C4-DC-activated DcuS-DcuR two-component system, and cAMP-CRP stimulate dctA expression. The expression of dctA is subject to the influence of various carbohydrates via cAMP-CRP, which differently modulate cAMP levels. Here we show that EIIAGlc of the glucose-specific phosphotransferase system strongly interacts with DctA, potentially resulting in the exclusion of C4-DCs when preferred carbon substrates, such as sugars, are present. In contrast to the classical inducer exclusion known for lactose permease LacY, inhibition of C4-DC uptake into the cytoplasm affects only its role as a substrate, but not as an inducer since DcuS detects C4-DCs in the periplasmic space (“substrate exclusion”). The work shows an interplay between cAMP-CRP and the DcuS-DcuR regulatory system for the regulation of dctA at both transcriptional and posttranslational levels. Conclusion: The study highlights a hierarchical interplay between global (cAMP-CRP) and specific (DcuS-DcuR) regulation of dctA at the transcriptional and posttranslational levels. The integration of global and specific transcriptional regulation of dctA, along with the influence of EIIAGlc on DctA, fine-tunes C4-DC catabolism in response to the availability of other preferred carbon sources. It attributes DctA a central role in the control of aerobic C4-DC catabolism and suggests a new role to EIIAGlc on transporters (control of substrate uptake by substrate exclusion).

Antimicrobial therapy based on self-assembling peptides.

The emergence of drug-resistant microorganisms has threatened global health, and microbial infections have severely limited the use of medical materials. For example, the attachment and colonization of pathogenic bacteria to medical implant materials can lead to wound infections, inflammation and complications, as well as implant failure, shortening their lifespan and even resulting in patient death. In the era of antibiotic resistance, antimicrobial drug discovery needs to prioritize unconventional therapies that act on new targets or adopt new mechanisms. In this regard, supramolecular antimicrobial peptides have emerged as attractive therapeutic platforms, both as bactericides for combination antibiotics and as delivery vehicles. By taking advantage of their programmable intermolecular and intramolecular interactions, peptides can be modified to form higher-order structures (including nanofibers and nanoparticles) with unique functionality. This paper begins with an analysis of the relationship between peptide self-assembly and antimicrobial activity, describes in detail the research and development of various self-assembled antimicrobial peptides in recent years, and finally explores different combinatorial strategies for self-assembling antimicrobial peptides.

A peptide selectively recognizes Gram-negative bacteria and forms a bacterial extracellular trap (BET) through interfacial self-assembly.

An innate immune system intricately leverages unique mechanisms to inhibit colonization of external invasive Bacteria, for example human defensin-6, through responsive encapsulation of bacteria. Infection and accompanying antibiotic resistance stemming from Gram-negative bacteria aggregation represent an emerging public health crisis, which calls for research into novel anti-bacterial therapeutics. Herein, inspired by naturally found host-defense peptides, we design a defensin-like peptide ligand, bacteria extracellular trap (BET) peptide, with modular design composed of targeting, assembly, and hydrophobic motifs with an aggregation-induced emission feature. The ligand specifically recognizes Gram-negative bacteria via targeting cell wall conserved lipopolysaccharides (LPS) and transforms from nanoparticles to nanofibrous networks in situ to trap bacteria and induce aggregation. Importantly, treatment of the BET peptide was found to have an antibacterial effect on the Pseudomonas aeruginosa strain, which is comparable to neomycin. Animal studies further demonstrate its ability to trigger aggregation of bacteria in vivo. This biomimetic self-assembling BET peptide provides a novel approach to fight against pathogenic Gram-negative bacteria.

Lactobacillus plantarum 69-2 combined with α-lactalbumin hydrolysate alleviates DSS-induced ulcerative colitis through the TLR4/NF-κB inflammatory pathway and the gut microbiota in mice.

Ulcerative colitis (UC), an inflammatory bowel disease, seriously affects people's quality of life. Diet-derived active peptides and Lactobacillus plantarum have shown promise for mitigating symptoms of UC. This investigation explored the combined effects of α-lactalbumin (α-LA) hydrolysate, which boasts a high antioxidant capacity, and L. plantarum 69-2 (L69-2) on a colitis mouse model. The results showed that α-LA hydrolysate with a molecular weight <3 kDa obtained with neutral protease had excellent antioxidant activity and potential to enhance probiotic proliferation. Furthermore, the synergistic application of α-LA hydrolysate and L69-2 could alleviate the adverse impact of colon inflammation by reducing oxidative stress and regulating immune disorders. It maintains the intestinal epithelial barrier, thereby reducing immune system over-activation, promoting the colonization of beneficial bacteria, and regulating intestinal immune responses. Simultaneously, it remodels the structure of the disrupted intestinal flora. The increase in the richness and diversity of the flora leads to the production of beneficial metabolites, which in turn inhibits the activation of the TLR4/NF-κB inflammatory pathway. This study provides a novel perspective on milk-derived peptide synergism with probiotics in alleviating UC.

Select Gut Microbiota Impede Rotavirus Vaccine Efficacy

The protection provided by rotavirus (RV) vaccines is highly heterogeneous among individuals. We hypothesized that microbiota composition might influence RV vaccine efficacy. First, we examined the potential of segmented filamentous bacteria (SFB) colonization to influence RV vaccine efficacy in mice. Next, we probed the influence of human microbiomes on RV vaccination via administering mice fecal microbial transplants (FMTs) from children with robust or minimal RV vaccine responsiveness. Post-FMT, mice were subjected to RV vaccination followed by RV challenge. SFB colonization induced a phenotype that was reminiscent of RV vaccine failure (ie, failure to generate RV antigens and, consequently, anti-RV antibodies following RV vaccination resulting in proneness to RV challenge after SFB levels diminished). FMTs from children to mice recapitulated donor vaccination phenotype. Specifically, mice receiving FMTs from high-responsive vaccinees copiously shed RV antigens and robustly generated anti-RV antibodies following RV vaccination. Concomitantly, such mice were impervious to RV challenge. In contrast, mice receiving FMTs from children who had not responded to RV vaccination exhibited only modest responses to RV vaccination and, concomitantly, remained prone to RV challenge. Microbiome analysis ruled out a role for SFB but suggested involvement of Clostridium perfringens. Oral administration of cultured C.perfringens to gnotobiotic mice partially recapitulated the RV vaccine non-responder phenotype. Analysis of published microbiome data found C.perfringens abundance in children modestly associated with RV vaccine failure. Microbiota composition influences RV vaccine efficacy with C.perfringens being one, perhaps of many, potential contributing taxa.

Quaternary ammonium-tethered hyperbranched polyurea nanoassembly synergized with antibiotics for enhanced antimicrobial efficacy.

The effective transportation of antibiotics to bacteria embedded within a biofilm consisting of a dense matrix of extracellular polymeric substances is still a challenge in the treatment of bacterial biofilm associated infections. Here, we developed an antibiotic nanocarrier constructed from quaternary ammonium-tethered hyperbranched polyureas (HPUs-QA), which showed high loading capacity for a model antibiotic, rifampicin, and high efficacy in the transportation of rifampicin to biofilms. The rifampicin-loaded HPUs-QA nanoassembly (HPUs-Rif/QA) demonstrated a synergistic antimicrobial effect in killing planktonic bacteria and eradicating the corresponding biofilms. Compared to the treatment of bacteria-infected chronic wounds by either HPUs-QA or rifampicin alone, HPUs-Rif/QA showed superior efficacy in promoting wound healing by more effectively inhibiting bacteria colonization. This study highlights the potential of the HPUs-QA nanoassembly in synergistic action with antibiotics for the treatment of biofilm associated infections.

Effect of acetic acid bacteria colonization on oviposition and feeding site choice in Drosophila suzukii and its related species.

Unlike many species of Drosophila flies that colonize decaying fruits, Drosophila suzukii lay eggs in ripening fruits. The oviposition and feeding site preferences for bacterial growth were quantified in multiple strains of D. suzukii and its closely related species, D. subpulchrella and D. biarmipes . A continuous degree of preference for oviposition sites with Acetobacter growth both within and across species suggested that the separation in resource usage is notable but not complete among these species. The lack of interspecific differences in feeding site preference for Acetobacter -containing media implied that the oviposition site preferences evolved independently from the feeding site preference.

Helicobacter pylori-Induced Angiopoietin-Like 4 Promotes Gastric Bacterial Colonization and Gastritis.

Helicobacter pylori infection is characterized as progressive processes of bacterial persistence and chronic gastritis with features of infiltration of mononuclear cells more than granulocytes in gastric mucosa. Angiopoietin-like 4 (ANGPTL4) is considered a double-edged sword in inflammation-associated diseases, but its function and clinical relevance in H. pylori-associated pathology are unknown. Here, we demonstrate both pro-colonization and pro-inflammation roles of ANGPTL4 in H. pylori infection. Increased ANGPTL4 in the infected gastric mucosa was produced from gastric epithelial cells (GECs) synergistically induced by H. pylori and IL-17A in a cagA-dependent manner. Human gastric ANGPTL4 correlated with H. pylori colonization and the severity of gastritis, and mouse ANGPTL4 from non-bone marrow-derived cells promoted bacteria colonization and inflammation. Importantly, H. pylori colonization and inflammation were attenuated in Il17a -/-, Angptl4 -/-, and Il17a -/- Angptl4 -/- mice. Mechanistically, ANGPTL4 bound to integrin αV (ITGAV) on GECs to suppress CXCL1 production by inhibiting ERK, leading to decreased gastric influx of neutrophils, thereby promoting H. pylori colonization; ANGPTL4 also bound to ITGAV on monocytes to promote CCL5 production by activating PI3K-AKT-NF-κB, resulting in increased gastric influx of regulatory CD4+ T cells (Tregs) via CCL5-CCR4-dependent migration. In turn, ANGPTL4 induced Treg proliferation by binding to ITGAV to activate PI3K-AKT-NF-κB, promoting H. pylori-associated gastritis. Overall, we propose a model in which ANGPTL4 collectively ensures H. pylori persistence and promotes gastritis. Efforts to inhibit ANGPTL4-associated pathway may prove valuable strategies in treating H. pylori infection.