The Effects of Probiotics, Prebiotics, and Synbiotics on Wound Infection: A Systematic Review.

INTRODUCTION: This systematic review aimed to summarize the currently available evidence on the effect of oral probiotic therapy on infected wound healing among patients who underwent surgery. MATERIALS AND METHODS: An electronic search was conducted for articles published during 2010- 2022 in Embase, PubMed/Medline, Scopus, Web of Science, and Google Scholar using the keywords "probiotics," "prebiotics," "synbiotics," and "wound infection." The titles and abstracts of 2625 articles were screened, and 22 publications that fulfilled the inclusion criteria were included. RESULTS: The current review provides evidence of the beneficial effects of probiotics on wound infection, significantly reducing the duration of antibiotic usage and the length of hospital stay for patients, with no serious side effects reported. Wound infections following various surgeries, such as abdominal wound surgery, colorectal cancer resection, periampullary neoplasms treatment, liver and bile duct resection, pancreaticoduodenectomy, esophagostomy, dental wound surgery, plastic surgery, and burns, are shown to be positively affected by probiotic usage. Although, in some cases, the improvements were not statistically significant, overall, the administration of probiotics appears to be satisfactory in this regard. CONCLUSION: Probiotics demonstrate the ability to prevent the growth of pathogens and maintain wound space sterility by recruiting M2 macrophages, which produce anti-inflammatory markers and enhance the activity of phagocytic cells. Additionally, probiotics can reduce bacterial translocation from their niche to other areas and inhibit the production of bacterial mediators that lead to bacterial invasion.

The effects of Fasciola hepatica recombinant proteins (peroxiredoxin and cathepsin L1) on Crohn's disease experimental model.

The immunomodulatory potential of the excretory-secretory (E/S) proteins of the helminths has been shown in previous investigations. This study evaluated the effects of the recombinants and excretory-secretory proteins of the Fasciola hepatica on induced colitis in Balb/c mice. The F. hepatica Recombinant proteins, Cathepsin L1 and Peroxiredoxin, and E/S proteins were intraperitoneally injected into the three mice groups as the case groups, while the control groups received PBS. Colitis was induced in mice by intraluminal administration of the 2, 4, 6-Trinitrobenzenesulfonic acid solution (TNBS). After 8 h, the case groups received the second dosage of the treatments, and it was repeated 24 h later. The immunological, pathological, and macroscopic changes were evaluated 3 days after colitis induction. The macroscopic evaluation revealed significantly lower inflammatory scores in the mice treated with recombinant Peroxiredoxin (rPRX) and recombinant Cathepsin L1 (rCL1). Despite the macroscopic observation, the pathological finding was insignificant between the groups. IFN-γ secretion was significantly lower in splenocytes of the groups that received rPRX, rCL1, and E/S than the controls. IL-10 showed significantly higher levels in groups treated with rPRX and rCL1 than controls, whereas the level of IL-4 was not statistically significant. Excretory-secretory proteins of the F. hepatica showed immunomodulatory potency and the main effects observed in this study were through the reduction of inflammatory cytokine and inflammation manifestation as well as induction of anti-inflammatory cytokines.

In silico Study of the Proteins Involved in the Persistence of Brucella spp.

BACKGROUND: One of the major problems with Brucella infections is its tendency to become chronic and recurrent, providing a hindrance to the management of this infection. It has been proposed that chronicity is greatly affected by a phenomenon called persistence in bacteria. Several mechanisms are involved in bacterial persistence, including the type II toxin-antitoxin system, the SOS and oxidative and stringent responses. METHODS: In this in silico study, these persistence mechanisms in Brucella spp. were investigated. RESULTS: The structure and the interactions between modules involved in these systems were designed, and novel peptides that can interfere with some of these important mechanisms were developed. CONCLUSION: Since peptide-based therapeutics are a new and evolving field due to their ease of production, we hope that peptides developed in this study, as well as the information about the structure and interactions of modules of persistence mechanisms, can further be used to design drugs against Brucella persister cells in the hope of restraining the chronic nature of Brucellosis.

In Vitro and In Silico Investigation of some Type II TA Genes in H. Pylori.

BACKGROUND: In addition to antibiotic resistance, the entry of Helicobacter pylori into the persistence phase leads to recurrent and chronic infections, as well as the development of antibiotic resistance in persister cells. METHODS: In this study, after genetic confirmation of H. pylori in 20 biopsy specimens, the prevalence of the type II TA systems mazEF, relEB, yafQ/dinJ was investigated. Also, the most common system observed in the study in terms of structure, evolution, and molecular interaction was evaluated by bioinformatics tools. RESULTS: The results of the PCR test on 20 biopsy samples were positive for ureA and glmM genes. Moreover, yafQ/ dinJ was the only module positive in half of the samples (10 samples) in the PCR technique. The toxin residues and their interactions with the cognate antitoxin residues are revealed by docking analysis results. Furthermore, the multiple sequence alignment (MSA) of the YafQ toxin showed that this toxin has a low polymorphism among H. pylori species. The evolutionary study showed that the yafQ toxin had the highest sequence similarity among the bacteria Helicobacter cetorm (60% similarity) and Muricauda olearia (57.35 % similarity). CONCLUSIONS: Collectively, the data of the present study indicate that the YafQ/DinJ is the dominant type II TA system and has the highest frequency among the studied systems in H. pylori, and further studies are required to elucidate its exact role in this bacterium.

Correction: Anti-cancer effects of Bifidobacterium species in colon cancer cells and a mouse model of carcinogenesis.

[This corrects the article DOI: 10.1371/journal.pone.0232930.].

Correction: Anti-cancer effects of Bifidobacterium species in colon cancer cells and a mouse model of carcinogenesis.

[This corrects the article DOI: 10.1371/journal.pone.0232930.].

Anti-cancer effects of Bifidobacterium species in colon cancer cells and a mouse model of carcinogenesis.

INTRODUCTION: Probiotics are suggested to prevent colorectal cancer (CRC). This study aimed to investigate the anticancer properties of some potential probiotics in vitro and in vivo. MATERIALS AND METHODS: Anticancer effects of the following potential probiotic groups were investigated in LS174T cancer cells compared to IEC-18 normal cells. 1. a single strain of Bifidobacterium. breve, 2. a single strain of Lactobacillus. reuteri, 3. a cocktail of 5 strains of Lactobacilli (LC), 4. a cocktail of 5 strains of Bifidobacteria (BC), 5. a cocktail of 10 strains from Lactobacillus and Bifidobacterium (L+B). Apoptosis rate, EGFR, HER-2 and PTGS-2 (COX-2 protein) expression levels were assessed as metrics of evaluating anticancer properties. Effect of BC, as the most effective group in vitro, was further assessed in mice models. RESULTS: BC induced ~21% and only ~3% apoptosis among LS174T and IEC-18 cells respectively. BC decreased the expression of EGFR by 4.4 folds, HER-2 by 6.7 folds, and PTGS-2 by 20 folds among the LS174T cells. In all these cases, BC did not interfere significantly with the expression of the genes in IEC-18 cells. This cocktail has caused only 1.1 folds decrease, 1.8 folds increase and 1.7 folds decrease in EGFR, HER-2 and PTGS-2 expression, respectively. Western blot analysis confirmed these results in the protein level. BC significantly ameliorated the disease activity index, restored colon length, inhibited the increase in incidence and progress of tumors to higher stages and grades. CONCLUSIONS: BC was the most efficient treatment in this study. It had considerable "protective" anti-cancer properties and concomitantly down regulated EGFR, HER-2 and PTGS-2 (COX-2), while having significant anti-CRC effects on CRC mice models. In general, this potential probiotic could be considered as a suitable nutritional supplement to treat and prevent CRC.

Lactobacillus species inhibitory effect on colorectal cancer progression through modulating the Wnt/ß-catenin signaling pathway.

Probiotic bacteria are known to exert a wide range of anticancer activities on their animal hosts. In the present study, the anticancer effect of a cocktail of several potential probiotic Lactobacillus species (potential probiotic L.C) was investigated in vitro and in vivo. MTT and Flow cytometry tests results showed that administration of live potential probiotic L.C significantly decreased the HT-29 and CT-26 cells proliferation and induced late apoptotis in a time-dependent manner. In addition, quantitative real-time polymerase chain reaction (qPCR) results showed that exposure of potential probiotic L.C to both HT-29 and CT-26 cells during the incubation times resulted in the upregulation (apc and CSNK1ε for HT-29, CSNK1ε and gsk3ß for CT-26) and downregulation (CTNNB1, CCND1, pygo2, axin2 and id2) of the Wnt/ß- catenin pathway-related genes in a time-dependent manner. The significance of in vitro anticancer effect of potential probiotic L.C was further confirmed in an experimental tumor model. Data from the murine model of colorectal cancer (CRC) induced by Azoxymethane (AOM) and Dextran Sulfate Sodium (DSS) showed significantly alleviated inflammation and tumor development in AOM/DSS/L.C-injected mice compared to the AOM/DSS-injected mice. Tumor growth inhibition was accompanied by potential probiotic L.C-driven upregulation and downregulation of the Wnt/ß-catenin pathway-related genes, similar to the in vitro results. These results showed that potential probiotic L.C inhibited the tumor growth, and that its anticancer activity was at least partially mediated through suppressing the Wnt/ß-catenin pathway. Overall, the present study suggested that this probiotic could be used clinically as a supplement for CRC prevention and treatment.

Inhibitory effects of Lactobacilli cocktail on HT-29 colon carcinoma cells growth and modulation of the Notch and Wnt/ß-catenin signaling pathways.

Probiotics could be considered as attractive candidates for preventing tumor growth through maintaining homeostasis. The aim of this study was to evaluate the inhibitory effect of a cocktail of five Lactobacillus species on human colorectal carcinoma cell line HT-29. The anti-proliferative and apoptotic effects of Lactobacilli cocktail were evaluated using MTT and flow cytometry tests, respectively. Quantitative real-time polymerase chain reaction (qPCR) was used to analyze the expression of several genes in the Notch (notch, hes1, msi1, and numb) and Wnt/ß-catenin (CTNNB1 and CCND1) pathways, following the treatment of HT-29 cells with Lactobacilli cocktail. The treatment by Lactobacilli cocktail induced a significant anti-proliferative effect and late stage apoptosis among the cancer cells (p < 0.05). Compared to the untreated cells, Lactobacilli cocktail induced the down-regulation of notch, hes1, and msi1 genes and up-regulation of numb gene in the Notch pathway as well as the down-regulation of CTNNB1 and CCND1 genes in the Wnt/ß-catenin pathway in a time-dependent manner (p < 0.05). CONCLUSION: Lactobacilli cocktail was shown to have beneficial anti-tumor effects on HT-29 cells by modulating the Notch and Wnt/ß-catenin pathways; therefore, the use of Lactobacilli probiotics as nutritional supplements may prevent the incidence of colon cancer.

A self-assessment predictive model for type 2 diabetes or impaired fasting glycaemia derived from a population-based survey.

AIMS: There is no cure for diabetes and its prevention is interesting for both people and health policy makers. The aim of this study was to construct a simple scoring system to predict diabetes and suggest a self assessment predictive model for type 2 diabetes in Iran. METHODS: This study was a part of a comprehensive population based survey performed in Ilam province during 2011-2012, including 2158 cases≥25years. All demographic and laboratory results were entered into the prepared sheets and were analysed using SPSS 16. By identification of relative risks of diabetes and IFG, a predictive model was constructed and proposed for these abnormalities. RESULTS: Totally, 2158 people comprising 72% female, 60% from urban regions, mean age of 45.5±14years were investigated and the average height, weight, FBS and waist of participants were as follows respectively: 164±8.9cm, 68.4±12.3kg, 5.7±2.8mmol/l (102.6±49.9mg/dl) and 82.3±14.3cm. The prevalence of IFG, diabetes and hyperglycaemia among all participants were 7.8%, 11.8% and 19.6% respectively. Regression analysis revealed familial history of diabetes, place of life, age, hypertension, daily exercise, marital status, gender, waist size, smoking, and BMI as the most relevant risk factors for diabetes and hyperglycemia. CONCLUSION: A self-assessment predictive model was constructed for general population living in the west of Iran. This is the first self-assessment predictive model for diabetes in Iran.

Hyperglycaemia and its related risk factors in Ilam province, west of Iran- a population-based study.

BACKGROUND: Impaired fasting glycaemia (IFG) has been defined as the fasting plasma glucose level between 6.1 (110 mgl/dl) and 6.9 mmol/l (125 mgl/dl). Control of hyperglycaemia during acute illness among diabetic and non-diabetic patients has been associated with improved outcome. The aim of this study was to investigate the prevalence of and factors related to hyperglycaemia, IFG and diabetes in west of Iran. METHODS: This project was performed by a cross-sectional method in Ilam province including 2158 people ≥ 25 years old. From the list of all rural and urban health centers of each county, several were randomly selected. For each selected health centre, families numbered 1-20 completed questionnaire forms for all the members aging ≥ 25 years. FBS was measured for all the participants by standard method. All the demographic and laboratory results were analysed using SPSS 16. Descriptive and regression analysis were used for statistical analysis appropriately. RESULTS: A total of 2158 people were evaluated in this study, among which 72 % were female with a mean age of 45.5 ± 14 years. 40 % of participants were from urban regions and the mean height, weight, FBS and waist size of the participants were respectively as follows: 164 ± 8.9 cm, 68.4 ± 12.3 kg, 5.7 ± 2.8 mmol/l (102.6 ± 49.9 mg/dl) and 82.3 ± 14.3 cm. The prevalence of IFG, diabetes and hyperglycaemia among participants were 7.8 %, 11.8 % and 19.6 %, respectively and participants from urban area showed a significantly higher prevalence of hyperglycaemia compared to rural regions (P < 0.0001). CONCLUSION: The most effective factors associated with IFG and diabetes were family history of diabetes, age, hypertension, marital status, place of life and smoking, respectively. The prevalence of IFG, diabetes and hyperglycemia among the population living in Ilam province, west of Iran, were 7.8, 11.8 and 19.6 % respectively which were directly increased with age.

Evaluation of biofilm production and characterization of genes encoding type III secretion system among Pseudomonas aeruginosa isolated from burn patients.

Pseudomonas aeruginosa is one of the common pathogenic causes of serious infections in burn patients throughout the world. Type III secretion toxins are thought to promote the dissemination of P. aeruginosa from the site of infection, the bacterial evasion of the host immune response and inhibition of DNA synthesis leading to host cell death. A total of 96 isolates of P. aeruginosa were collected from wound infections of burn patients, from April to July 2010. Antimicrobial susceptibility of the isolates were determined by disk agar diffusion method. Polymerase chain reaction (PCR)-based method was used for targeting the genes encoding the type III secretion toxins. The quantitative determination of biofilm-forming capacity was determined by a colorimetric microtiter plate assay. All the isolates were resistant to cefixime and ceftriaxone. More than 90% of the isolates were resistant to amikacin, carbenicillin, cefepime, cefotaxime, cefpodoxime, gatifloxacin, gentamicin, piperacillin/tazobactam, ticarcillin and tobramycin. All the isolates carried the exoT gene, 95% carried exoY, 64.5% carried exoU and 29% carried the exoS gene. Most of the isolates (58%) carried both exoY and exoU genes while 24% showed the concomitant presence of exoS and exoY and 1% carried both exoS and exoU. Coexistence of exoS, exoY and exoU was seen in 4% of the isolates. Biofilm formation was seen in more than 96% of the isolates among which 47% were strong biofilm producers, 26% were moderate and 22.9% were weak biofilm formers. In conclusion, the findings of this study show that the genes, particularly the exoU gene, encoding the type III secretion toxins, are commonly disseminated among the P. aeruginosa strains isolated from burn patients.