Microbiota insights into pet ownership and human health.

The relationship between pet and owner has already been studied in several studies. Reviewing and summarizing studies on human and pet microbiota and their effects due to keeping pets is the purpose of the current study. Microbiota of the gut, oral cavity, and skin are unique to each individual, and this is also true of their pets (cats and dogs). Microbiota homeostasis is essential for the health of pets and their owners. Dysbiosis or imbalances in the microbiota can increase the risk of disorder progressions such as IBD or Clostridium difficile infections, among others. The microbial communities of humans change as a result of various factors, such as keeping pets. Pet owners frequently contact domestic dogs and cats, which affects their microbiota. As a result of keeping pets, the microbiota of different areas of the human body has changed, which has been associated with a decrease in pathogenic bacteria and an increase in beneficial bacteria.

Tuberculosis and lung cancer: metabolic pathways play a key role.

Despite the fact that some cases of tuberculosis (TB) are undiagnosed and untreated, it remains a serious global public health issue. In the diagnosis, treatment, and control of latent and active TB, there may be a lack of effectiveness. An understanding of metabolic pathways can be fundamental to treat latent TB infection and active TB disease. Rather than targeting Mycobacterium tuberculosis, the control strategies aim to strengthen host responses to infection and reduce chronic inflammation by effectively enhancing host resistance to infection. The pathogenesis and progression of TB are linked to several metabolites and metabolic pathways, and they are potential targets for host-directed therapies. Additionally, metabolic pathways can contribute to the progression of lung cancer in patients with latent or active TB. A comprehensive metabolic pathway analysis is conducted to highlight lung cancer development in latent and active TB. The current study aimed to emphasize the association between metabolic pathways of tumor development in patients with latent and active TB. Health control programs around the world are compromised by TB and lung cancer due to their special epidemiological and clinical characteristics. Therefore, presenting the importance of lung cancer progression through metabolic pathways occurring upon TB infection can open new doors to improving control of TB infection and active TB disease while stressing that further evaluations are required to uncover this correlation.

The occurrence rate of Haarlem and Beijing genotypes among Middle Eastern isolates of multi drug resistant Mycobacterium tuberculosis: A systematic review and meta-analysis.

Antibiotic resistance is a serious problem that poses a major challenge to tuberculosis control worldwide. Many developing countries still struggle with this infection in term of various aspects as it remains a major health concern. A number of developing countries are located in the Middle East, one of the world's most important regions. The control of this infection remains largely suboptimal despite intensive research in the field, and the mechanisms that lead to its progression have not yet been fully understood. Therefore, TB control must be amended through the identification of new strategies. For this reason, monitoring genetic characterizations of TB strains by molecular typing methods in different geographical regions can be important to setting local programs and global strategies to control TB infection. It is important to know the genotype of Mycobacterium tuberculosis strains to evaluate the occurrence of outbreaks and the transmission of this disease. Beijing and Haarlem genotypes are the most prevalent and, in these families, there is greater association with drug resistance, resulting in more severe forms of TB and higher levels of treatment failure than in other families. The current study is planned to systematically conduct a review using a meta-analysis to show the prevalence of Beijing and Haarlem genotypes in the Middle Eastern MDR-TB cases. M. tuberculosis strains pose particular epidemiological and clinical concerns as they can endanger tuberculosis control programs.

Evaluation of miR-let-7f, miR-125a, and miR-125b expression levels in sputum and serum samples of Iranians and Afghans with pulmonary tuberculosis.

Background and Objectives: The role of microRNAs (miRNAs) in tuberculosis infection is well established. As microRNAs are able to change expression profiles according to different conditions, they can be useful biomarkers. Iranians and Afghans with tuberculosis were studied for three immune-related miRNAs (miR-let-7f, miR-125a, and miR-125b). Materials and Methods: A total of 60 Iranian and Afghan patients with active pulmonary TB were enrolled in the Pulmonary Department of the Pasteur Institute of Iran. Serum and sputum samples were collected simultaneously from all participants. A Real-time PCR was conducted to detect differentially expressed miRNAs. Results: Iranian (P<0.0001) and Afghan (P<0.0001) serum samples and Afghan (P<0.0001) sputum samples overexpressed miR-125a, whereas Iranian sputum samples showed downregulation (P=0.0039). In both Iranian (P<0.0001; P=0.0007) and Afghan (P<0.0001; P<0.0001) serum and sputum samples, miR-125b was overexpressed. Furthermore, miR-let-7f down-regulation was observed in serum and sputum samples (P<0.0001), whereas Iranian sputum samples had no statistically significant differences (P=0.348). Conclusion: Overexpression of miR-125a and miR-125b has been detected in Iranian and Afghan samples. In both races, miR-let-7f downregulation has been confirmed. Identification of miRNA profiles under different conditions opens the door to evaluating potential new biomarkers for diagnosis, disease monitoring, and therapeutic markers in TB infection.

The impact of ACE2 polymorphisms (rs1978124, rs2285666, and rs2074192) and ACE1 rs1799752 in the mortality rate of COVID-19 in different SARS-CoV-2 variants.

BACKGROUND: Clinical severity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outcomes could be influenced by genetic polymorphisms in angiotensin I-converting enzyme (ACE1) and ACE2. This study aims to examine three polymorphisms (rs1978124, rs2285666, and rs2074192) on the ACE2 gene and ACE1 rs1799752 (I/D) in patients who have coronavirus disease 2019 (COVID-19) with various SARS-CoV-2 variants. METHODS: Based on polymerase chain reaction-based genotyping, four polymorphisms in the ACE1 and ACE2 genes have been identified in 2023 deceased patients and 2307 recovered patients. RESULTS: The ACE2 rs2074192 TT genotype was associated with the COVID-19 mortality in all three variants, whereas the CT genotype was associated with the Omicron BA.5 and Delta variants. ACE2 rs1978124 TC genotypes were related to COVID-19 mortality in the Omicron BA.5 and Alpha variants, but TT genotypes were related to COVID-19 mortality in the Delta variant. It was found that ACE2 rs2285666 CC genotypes were associated with COVID-19 mortality in Delta and Alpha variants, and CT genotypes in Delta variants. There was an association between ACE1 rs1799752 DD and ID genotypes in the Delta variant and COVID-19 mortality, whereas there was no association in the Alpha or Omicron BA.5 variants. In all variants of SARS-CoV-2, CDCT and TDCT haplotypes were more common. In Omicron BA.5 and Delta, CDCC and TDCC haplotypes were linked with COVID-19 mortality. In addition to COVID-19 mortality, the CICT, TICT, and TICC were significantly correlated. CONCLUSION: The ACE1/ACE2 polymorphisms had an impact on COVID-19 infection, and these polymorphisms had different effects in various SARS-CoV-2 variants. To confirm these results, however, more research needs to be conducted.

Molecular epidemiology of nontuberculous mycobacteria isolated from tuberculosis-suspected patients.

It is a growing problem around the world to deal with nontuberculous mycobacteria infection (NTM), but its clinical significance is still largely unknown. This study aims to investigate the epidemiology of NTM infections from various clinical samples and determine their clinical significance. From December 2020 to December 2021, 6125 clinical samples were collected. In addition to phenotypic detection, genotypic detection through multilocus sequence typing (hsp65, rpoB, and 16S rDNA genes) and sequencing was also conducted. Records of patients were consulted for clinical information, such as symptoms and radiological findings. Of the 6,125 patients, 351 (5.7%) were positive for acid-fast bacteria (AFB). Out of 351 AFB, 289 (82.3%) and 62 (17.7%) subjects were identified as M. tuberculosis complex (MTC) and NTM strains, respectively. Isolates of Mycobacterium simiae and M. fortuitum were the most frequent, followed by isolates of M. kansasii and M. marinum. We also isolated M. chelonae, M. canariasense, and M. jacuzzii, which are rarely reported. Symptoms (P = 0.048), radiographic findings (P = 0.013), and gender (P = 0.039) were associated with NTM isolates. M. Fortuitum, M. simiae, and M. kansasii presented with bronchiectasis, infiltration, and cavitary lesions most frequently, while cough was the most common symptom. In conclusion, Mycobacterium simiae and M. fortuitum were presented in seventeen and twelve NTM isolates from the collected samples. There is evidence that NTM infections in endemic settings may contribute to the dissemination of various diseases and the control of tuberculosis. In spite of this, further research is needed to evaluate the clinical significance of NTM isolates.

Mixed pulmonary infection with four isolates of nontuberculous mycobacteria: a case report of mycobacterium bacteremicum infection.

BACKGROUND: A mixed pulmonary infection of Mycobacterium bacteremicum and three different isolates of nontuberculous mycobacteria (NTM) is an unusual clinical manifestation and have not yet been indicated. In this case report, we reported four isolates of NTM using phenotypic and genotypic test of pulmonary sample in Tehran, Iran. CASE PRESENTATION: We report a case of severe pulmonary disease in a 19-year-old male patient with productive cough, shortness of breath, and low-grade fever for several weeks. The C-reactive protein (CRP) level (80.2 mg/L) and erythrocyte sedimentation rate (ESR) (95 mm/h) were high. The computed tomographic scan indicated bronchiectasis, nodular opacities, consolidation, and cavitary lesions on both sides. The result of purified protein derivative (PPD) test was equal to 15 mm. The sequences of hsp65, rpoB, and 16S rDNA genes indicated more than 99% homology to four isolates of nontuberculous mycobacteria (NTM), including Mycobacterium fortuitum, M. chelonae, M. mucogenicum, and M. bacteremicum. We found that all four strains were susceptible to amikacin, cefoxitin, ciprofloxacin, clarithromycin, imipenem, and linezolid. The patient was treated with ciprofloxacin, clarithromycin, and amikacin, along with Montelukast, for five months. CONCLUSION: We report a case of severe pulmonary infection by four isolates of NTM. After treatment, the patient reported complete resolution of the signs and a weight gain of 5 kg; also, the CRP and ESR were normal. Nine months after the infection diagnosis, a new CT scan revealed further improvements.

The global scientific publications on gut microbiota in type 2 diabetes; a bibliometric, Scientometric, and descriptive analysis.

Background: Modifying gut dysbiosis has achieved great success in managing type 2 diabetes mellitus (T2DM) and also T2DM affected the gut microbial composition. Objectives: To determine the research trend of scientific publications on the relationship between gut microbiota and T2DM through a bibliometric and descriptive approach. Method: We included originals and reviews related to both topics of gut microbiota and T2DM through searching in Scopus up to 31 December 2019 and then characterized their bibliometric profiles including the number of publications, citations, institutions, journals, countries, and the collaboration network of authors, countries, terms and keywords. Moreover, we performed a descriptive evaluation of the clinical trials based on their intervention type and its influence on gut dysbiosis. Results: We achieved 877 articles (436 originals and 441 reviews) according to our inclusion criteria. The annual publications were constantly increased over time and reached 220 publications in 2019. Out of 436 original articles, 231 animal studies and 174 human studies were found. The majority of human studies were clinical trials (n = 77) investigating the influence of drugs (n = 21), regimens (n = 21), pre/pro/symbiotic (n = 19), surgeries (n = 15), or both drug and regimen (n = 1) on gut dysbiosis. Roux-en-Y gastric bypass and metformin were assessed the most in these trials. Obesity side by side T2DM has been assessed in this area of literature based on term and keyword analyses showing their possible similar pathways mediated by gut microbiota. Conclusion: The exponentially growing documents on gut microbiota and T2DM had been published during the last decade and revealed gut microbiota alteration mediated antidiabetic effect of many interventions. Thus, we suggest other researchers to consider this pathway in efficacy assessment of therapeutic modalities and to find the optimal composition of gut microbiota that guarantees healthy insulin sensitivity. Supplementary Information: The online version contains supplementary material available at 10.1007/s40200-021-00920-1.

Nontuberculous Mycobacterial Resistance to Antibiotics and Disinfectants: Challenges Still Ahead.

The mortality incidence from nontuberculous mycobacteria (NTM) infections has been steadily developing globally. These bacterial agents were once thought to be innocent environmental saprophytic that are only dangerous to patients with defective lungs or the immunosuppressed. Nevertheless, the emergence of highly resistant NTM to different antibiotics and disinfectants increased the importance of these agents in the health system. Currently, NTM frequently infect seemingly immunocompetent individuals at rising rates. This is of concern as the resistant NTM are difficult to control and treat. The details behind this NTM development are only beginning to be clarified. The current study will provide an overview of the most important NTM resistance mechanisms to not only antibiotics but also the most commonly used disinfectants. Such evaluations can open new doors to improving control strategies and reducing the risk of NTM infection. Moreover, further studies are crucial to uncover this association.

Commensal and Pathogenic Bacterial-Derived Extracellular Vesicles in Host-Bacterial and Interbacterial Dialogues: Two Sides of the Same Coin.

Extracellular vesicles (EVs) cause effective changes in various domains of life. These bioactive structures are essential to the bidirectional organ communication. Recently, increasing research attention has been paid to EVs derived from commensal and pathogenic bacteria in their potential role to affect human disease risk for cancers and a variety of metabolic, gastrointestinal, psychiatric, and mental disorders. The present review presents an overview of both the protective and harmful roles of commensal and pathogenic bacteria-derived EVs in host-bacterial and interbacterial interactions. Bacterial EVs could impact upon human health by regulating microbiota-host crosstalk intestinal homeostasis, even in distal organs. The importance of vesicles derived from bacteria has been also evaluated regarding epigenetic modifications and applications. Generally, the evaluation of bacterial EVs is important towards finding efficient strategies for the prevention and treatment of various human diseases and maintaining metabolic homeostasis.

RNA Expression Analysis of Mycobacterial Methyltransferases Genes in Different Resistant Strains of Mycobacterium tuberculosis.

Background: Tuberculosis infection still represents a global health issue affecting patients worldwide. Strategies for its control may be not as effective as it should be, specifically in case of resistant strains of Mycobacterium tuberculosis (M.tb.) In this regard, the role of mycobacterial methyltransferases (MTases) in TB infection can be fundamental, though it has not been broadly deciphered. Methods: Five resistant isolates of M.tb were obtained. M.tb H37Rv (ATCC 27249) was used as a reference strain. Seven putative mycobacterial MTase genes (Rv0645c, Rv2966c, Rv1988, Rv1694, Rv3919c, Rv2756c, and Rv3263) and Rv1392 as SAM synthase were selected for analysis. PCR-sequencing and qRT-PCR were performed to compare mutations and expression levels of MTases in different strains. The 2-ΔΔCt method was employed to calculate the relative expression levels of these genes. Results: Only two mutations were found in isoniazid resistance (INHR) strain for Rv3919c (T to G in codon 341) and Rv1392 (G to A in codon 97) genes. Overexpression of Rv0645c, Rv2756c, Rv3263, and Rv2966c was detected in all sensitive and resistant isolates. However, Rv1988 and Rv3919c decreased and Rv1694 increased in the sensitive strains. The Rv1392 expression level also decreased in INHR isolate. Conclusion: We found a correlation between mycobacterial MTases expression and resistance to antibiotics in M.tb strains. Some MTases undeniably are virulence factors that specifically hijack the host defense mechanism. Further evaluations are needed to explore the complete impact of mycobacterial MTases within specific strains of M.tb to introduce novel diagnosis and treatment strategies.

From the Role of Microbiota in Gut-Lung Axis to SARS-CoV-2 Pathogenesis.

Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) is responsible for the outbreak of a new viral respiratory infection. It has been demonstrated that the microbiota has a crucial role in establishing immune responses against respiratory infections, which are controlled by a bidirectional cross-talk, known as the "gut-lung axis." The effects of microbiota on antiviral immune responses, including dendritic cell (DC) function and lymphocyte homing in the gut-lung axis, have been reported in the recent literature. Additionally, the gut microbiota composition affects (and is affected by) the expression of angiotensin-converting enzyme-2 (ACE2), which is the main receptor for SARS-CoV-2 and contributes to regulate inflammation. Several studies demonstrated an altered microbiota composition in patients infected with SARS-CoV-2, compared to healthy individuals. Furthermore, it has been shown that vaccine efficacy against viral respiratory infection is influenced by probiotics pretreatment. Therefore, the importance of the gut microbiota composition in the lung immune system and ACE2 expression could be valuable to provide optimal therapeutic approaches for SARS-CoV-2 and to preserve the symbiotic relationship of the microbiota with the host.

The inter-talk between Mycobacterium tuberculosis and the epigenetic mechanisms.

Epigenetics regulate gene function without any alteration in the DNA sequence. The epigenetics represent one of the most important regulators in different cellular processes and have initially been developed in microorganisms as a protective strategy. The evaluation of the epigenetic mechanisms is also important in achieving an efficient control strategy in tuberculosis (TB). TB is one of the most significant epidemiological concerns in human history. Despite several in vivo and in vitro studies that have evaluated different epigenetic modifications in TB, many aspects of the association between epigenetics and TB are not fully understood. The current paper is aimed at reviewing our knowledge on histone modifications and DNA methylation modifications, as well as miRNAs regulation in TB.

The First Report of Differences in Gut Microbiota Composition between Obese and Normal Weight Iranian Subjects

Background: OObesity is a complex disorder influenced by various genetic and environmental factors. It has been shown that gut microbiota, which colonizes gastrointestinal tract, has a substantial role as an environmental factor in the pathophysiology of obesity. Since the composition of gut microbiota alters with regard to different criteria, such as ethnicity, geographical location, diet, lifestyle, age, and gender, we aimed to determine firmicutes/bacteroidetes (F/B) ratio and the abundance of important gut microbiota members, Akkermansia muciniphila, Faecalibacterium prausnitzii, Roseburia, Bifidobacterium, and Prevotella in Iranian obese and normal weight individuals, for the first time. Methods: In this study, 50 normal and 50 obese subjects were recruited and classified based on their BMI into normal weight and obese groups. Stool samples were collected. Following DNA extraction from the samples, quantitative PCR was conducted based on 16s rDNA universal primers. Finally, the correlation between the bacterial abundance and obesity was analyzed by statistical analyses. Results: We observed a significant increase of F/B ratio in the obese group, compared to the normal weight group (p = 0.002). Although A. muciniphila (p = 0.039) and Bifidobacterium (p = 0.049) abundance significantly decreased, the abundance of F. prausnitzii (p = 0.046) significantly elevated with BMI increase in the studied groups. Conclusion: Owing to the importance of the gut microbiota composition in obesity development, determination and targeted restoration of gut microbiota pattern could be valuable in the control and treatment of obesity in certain populations.

Gut Bacteria and their Metabolites: Which One Is the Defendant for Colorectal Cancer?

Colorectal cancer (CRC) is a worldwide health concern which requires efficient therapeutic strategies. The mechanisms underlying CRC remain an essential subject of investigations in the cancer biology field. The evaluation of human microbiota can be critical in this regard, since the disruption of the normal community of gut bacteria is an important issue in the development of CRC. However, several studies have already evaluated the different aspects of the association between microbiota and CRC. The current study aimed at reviewing and summarizing most of the studies on the modifications of gut bacteria detected in stool and tissue samples of CRC cases. In addition, the importance of metabolites derived from gut bacteria, their relationship with the microbiota, and epigenetic modifications have been evaluated.

Characterization of Phenotypic and Genotypic Diversity of Stenotrophomonas maltophilia Strains Isolated From Selected Hospitals in Iran.

Stenotrophomonas maltophilia is an environmental Gram-negative bacterium that has rapidly emerged as an important nosocomial pathogen in hospitalized patients. Treatment of S. maltophilia infections is difficult due to increasing resistance to multiple antibacterial agents. The purpose of this study was to determine the phenotypic and genotypic characterization of S. maltophilia isolates recovered from patients referred to several hospitals. A total of 164 clinical isolates of S. maltophilia were collected from hospitals in various regions in Iran between 2016 and 2017. Antibiotic susceptibility testing was performed by disc diffusion method and E-test assay according to the Clinical and Laboratory Standards Institute (CLSI) guideline. The ability of biofilm formation was assessed with crystal violet staining and then, biofilm-associated genes were investigated by PCR-sequencing method. The presence of L1 (a metallo-ß-lactamase), L2 (a clavulanic acid-sensitive cephalosporinase), sul1 and sul2 (resistance to Trimethoprim/Sulfamethoxazole), Smqnr (intrinsic resistance to quinolones), and dfrA genes (dihydrofolate reductase enzyme that contributes to trimethoprim resistance) was also examined by PCR-sequencing. Relative gene expression of smeDEF efflux pump was assessed by real-time PCR. Genotyping was performed using the multi-locus sequencing typing (MLST) and repetitive extragenic palindromic-PCR (Rep-PCR). Isolates were resistant to imipenem (100%), meropenem (96%), doripenem (96%), and ceftazidime (36.58%). Notably, 5 (3.04%) isolates showed resistant to trimethoprim-sulfamethoxazole (TMP-SMX), an alarming trend of decreased susceptibility to TMP-SMX in Iran. Minocycline and levofloxacin exhibited the highest susceptibility of 91.46 and 99.39%, respectively. Using the crystal violet staining, 157 (95.73%) isolates had biofilm phenotype: 49 (29.87%), 63 (38.41%), and 45 (27.43%) isolates were categorized as strong-, moderate- and weak-biofilm producer while 7 isolates (4.26%) were identified a non-biofilm producer. Biofilm genes had an overall prevalence of 145 (88.41%), 137 (83.53%), and 164 (100%) of rmlA, rpfF, and spgM, respectively. L1, L2, Smqnr, sul1, and sul2 resistance genes were detected in 145 (88.41%), 156 (96.12%), 103 (62.80%), 89 (54.26%), and 92 (56.09%) isolates, respectively. None of the S. maltophilia isolates were positive for dfrA12, dfrA17, and dfrA27 genes. Gene expression analysis showed that smeD efflux system was overexpressed in two out of the five clinical isolates (40%) that showed resistance to TMP-SMX. Most of the isolates were genetically unrelated. Two new sequence types (ST139 and ST259) were determined. Our results showed that TMP-SMX was still an effective antibiotic against S. maltophilia. The findings of the current study revealed an increasing prevalence of antibiotic resistance and biofilm genes in clinical S. maltophilia isolates in Iran.

The effect of saturated and unsaturated fatty acids on the production of outer membrane vesicles from Bacteroides fragilis and Bacteroides thetaiotaomicron.

AIM: The aim of present study is to investigate the effect of fatty acids on the outer membrane vesicles (OMVs) produced by Bacteroides spp. BACKGROUND: Bacteroides spp. is the important member of Gut microbiota that employ OMVs production for interact with host. Besides, dietary fatty acids could influence on determination of gut microbiota composition and immune response. In this regard, we evaluated the effect of fatty acids on the growth and OMVs production of Bacteroides fragilis and Bacteroides thetaiotaomicron. METHODS: B. fragilis and B. thetaiotaomicron were grown on BHI broth with and without palmitic and palmitoleic acids as saturated and unsaturated fatty acids, respectively. OMVs were extracted using multiple centrifugation and tris-ethylene diamine tetra acetic acid (EDTA)-Sodium deoxy cholate buffers. Physicochemical properties of OMVs were detected by electron microscopy (SEM), Bradford Coomassie brilliant blue assay and SDS-PAGE. Data were analyzed with One-way ANOVA using SPSS. RESULTS: The growths of both Bacteroides were significantly increased by palmitic acid. Nevertheless, palmitoleic acid had no significant effect on them. Palmitic acid significantly decreased and increased the production of B. fragilis OMVs at low and high concentration, respectively. However, the production of B. thetaiotaomicron OMVs was not significantly affected by palmitic acid. Although palmitoleic acid had a significant decreasing effect on the production of B. fragilis OMVs, it significantly increased the production of B. thetaiotaomicron OMVs at low concentration. CONCLUSION: In conclusion we reported that palmitic acid had a stimulatory effect on the growth of B. fragilis and B. thetaiotaomicron and had a dose dependent effect on the production of B. fragilis OMVs. Also producing of B. thetaiotaomicron OMVs was affected by palmitoleic acid in a dose dependent manner.

The human microbiota in pulmonary tuberculosis: Not so innocent bystanders.

Mycobacterium tuberculosis (Mtb) infection is a worldwide health concern, which needs robust and efficient control strategies, and the evaluation of human microbiota can be very important in this regard. Dysbiosis of normal microbiota is an important issue in the pathogenesis of Mtb. However, only few studies demonstrated the interaction between Mtb infection and microbiota. The current study aimed at reviewing literature on gut and lung microbiota in Mtb infection. Eleven articles regarding gut and lung microbiota composition in individuals with Mtb infection were selected, and then the importance of gut-lung axis in Mtb infection was evaluated. Also the relationship between microbiota composition and Mtb infection were discussed in terms of treatment, epigenetic field, and biomarkers.