New insight in molecular detection of Mycobacterium tuberculosis.

Mycobacterium tuberculosis, the causative agent of tuberculosis, is a pathogenic bacterium that has claimed millions of lives since the Middle Ages. According to the World Health Organization's report, tuberculosis ranks among the ten deadliest diseases worldwide. The presence of an extensive array of genes and diverse proteins within the cellular structure of this bacterium has provided us with a potent tool for diagnosis. While the culture method remains the gold standard for tuberculosis diagnosis, it is possible that molecular diagnostic methods, emphasis on the identification of mutation genes (e.g., rpoB and gyrA) and single nucleotide polymorphisms, could offer a safe and reliable alternative. Over the past few decades, as our understanding of molecular genetics has expanded, methods have been developed based on gene expansion and detection. These methods typically commence with DNA amplification through nucleic acid targeted techniques such as polymerase chain reaction. Various molecular compounds and diverse approaches have been employed in molecular assays. In this review, we endeavor to provide an overview of molecular assays for the diagnosis of tuberculosis with their properties (utilization, challenges, and functions). The ultimate goal is to explore the potential of replacing traditional bacterial methods with these advanced molecular diagnostic techniques.

Direct and macrophage stimulation mediated effects of active, inactive, and cell-free supernatant forms of Akkermansia muciniphila and Faecalibacterium duncaniae on hepcidin gene expression in HepG2 cells.

Hepcidin is a crucial regulator of iron homeostasis with protective effects on liver fibrosis. Additionally, gut microbiota can also affect liver fibrosis and iron metabolism. Although the hepatoprotective potential of Akkermansia muciniphila and Faecalibacterium duncaniae, formerly known as F. prausnitzii, has been reported, however, their effects on hepcidin expression remain unknown. We investigated the direct and macrophage stimulation-mediated effects of active, heat-inactivated, and cell-free supernatant (CFS) forms of A. muciniphila and F. duncaniae on hepcidin expression in HepG2 cells by RT-qPCR analysis. Following stimulation of phorbol-12-myristate-13-acetate (PMA) -differentiated THP-1 cells with A. muciniphila and F. duncaniae, IL-6 concentration was assessed via ELISA. Additionally, the resulting supernatant was treated with HepG2 cells to evaluate the effect of macrophage stimulation on hepcidin gene expression. The expression of genes mediating iron absorption and export was also examined in HepG2 and Caco-2 cells via RT-qPCR. All forms of F. duncaniae increased hepcidin expression while active and heat-inactivated/CFS forms of A. muciniphila upregulated and downregulated its expression, respectively. Active, heat-inactivated, and CFS forms of A. muciniphila and F. duncaniae upregulated hepcidin expression, consistent with the elevation of IL-6 released from THP-1-stimulated cells as a macrophage stimulation effect in HepG2 cells. A. muciniphila and F. duncaniae in active, inactive, and CFS forms altered the expression of hepatocyte and intestinal iron-mediated absorption /exporter genes, namely dcytb and dmt1, and fpn in HepG2 and Caco-2 cells, respectively. In conclusion, A. muciniphila and F. duncaniae affect not only directly but also through macrophage stimulation the expression of hepcidin gene in HepG2 cells. These findings underscore the potential of A. muciniphila and F. duncaniae as a potential therapeutic target for liver fibrosis by modulating hepcidin and intestinal and hepatocyte iron metabolism mediated gene expression.

The association between gut microbiota and resting metabolic rate in overweight/obese women: a case-control study.

Purpose: When examining the underlying processes of obesity, evaluation of gut flora and energy homeostasis can be crucial since disruption of the normal gut microbiota community and energy imbalances are significant factors in the development of obesity. Therefore, this study aimed to compare the relative abundance of important obesity modulator gut microbiota (including Firmicutes, Bacteroidetes, Bifidobactrium spp., Lactobacillus spp., Bacteroides fragilis, Faecalibacterium prausnitzii, Akkermansia muciniphila, and Escherichia coli) in fecal samples of normometabilic and hypometabolic overweight/obese individuals. Methods: This matched case-control study conducted on 36 healthy women aged 18-50 years old. An indirect calorimeter and impedance body analyzer were used to assess resting metabolic rate (RMR) and body composition, respectively. Dietary intake and physical activity were assessed using questionnaires. To determine the abundance of the abovementioned gut microbiota, quantitative polymerase chain reaction (qPCR) method was performed. Moreover, ELISA kits were used to assess leptin, ghrelin, and insulin hormones. Results: The results highlighted higher load of Firmicutes (p = 0.02), F. prausnitzii (p < 0.001), and B. fragilis (p = 0.02) in the normometabolic individuals compared to the hypometabolic ones. Besides, the positive correlation between the abundance of Firmicutes (ß = 7.76 × 10-1, p = 0.01), F. prausnitzii (ß = 1.29 × 10-5, p = 0.01), and B. fragilis (ß = 4.13 × 10-6, p = 0.04) with the RMR have been shown. Whereas the abundance of Bacteroidetes, A. muciniphila, Lactobacillus spp., Bifidobactrium spp., and E. coli showed no significant difference (p > 0.05) and no significant correlation with the RMR except Lactobacillus spp. (ß = 1.73 × 10-4, p = 0.01). Conclusion: It seems that gut microbiota can be a potential target for refining host energy homeostasis and treating obesity and its consequences.

Significance of genotypes and resistance status of Mycobacterium tuberculosis strains in gene expression of apoptosis cell death and inflammatory pathways in A549 lung epithelial cell line.

Objectives: Tuberculosis (TB) has been a major health issue throughout history. As part of TB infection, host-Mycobacterium tuberculosis (Mtb) interactions are important. Through immune pathology and cell death control processes, Mtb infection facilitates intracellular growth. The relationship between apoptosis and inflammation in Mtb infection remains unclear. In this study, the levels of related apoptosis and inflammatory genes were assessed in A549 cells infected with a variety of Mtb strains. Materials and Methods: Mtb isolates with different phenotypes (sensitive, INHR, RifR, MDR, and XDR) were collected from the Pasteur Institute of Iran, during this study. Whole genome sequencing was previously performed on all strains, and the Beijing genotype was selected as sensitive. Also, for other resistant strains, the New-1 genotype was available and isolated for genotype comparison. A549 lung carcinoma cells were also grown and infected with selected Mtb strains. Genes involved in inflammation and apoptosis were detected using reverse transcription-PCR (RT-PCR). Results: All sensitive strains and resistant strains were found to significantly up-regulate anti-apoptotic (bcl2 and rb1), chemokine (IL-8 and MCP-1), and pro-inflammatory cytokine (TNF-α and IFN-γ) expression, while significant down-regulation was observed after 24 and 48 hr of infection in anti-inflammatory genes (IL-10) and pro-apoptotic genes (bad and bax). Besides resistance strains, Mtb genotypes also affected gene expression. The Beijing genotype (sensitive isolate) influences inflammatory and apoptotic genes more sharply than the New-1 genotype (INHR, RifR, MDR, and XDR). Conclusion: Gene expression differences related to apoptosis and inflammation examined in the current study may be attributed to genotypes rather than resistance status since the expression of most genes has been observed to be lower in resistant strains (INHR, RifR, MDR, and XDR belonging to the New-1 genotype) compared to sensitive strains (Beijing genotype).

Gut-Lung Microbiota Characterization in Patients with Non-Small Cell Lung Carcinoma and COVID-19 Coinfection.

BACKGROUND: Non-small cell lung cancer (NSCLC) patients with COVID-19 have an excessive chance of morbidity and mortality. The fecal-nasopharyngeal microbiota compositions of NSCLC patients were assessed in this study. METHODS: In total, 234 samples were collected from 17 NSCLC patients infected with COVID-19, 20 NSCLC patients without confirmed COVID-19, 40 non NSCLC patients with COVID-19, and 40 healthy individuals. RESULTS: In lung microbiota, the abundance of Streptococcus spp. in NSCLC patients with confirmed COVID-19 was significantly higher than the two control groups. Pseudomonas aeruginosa and Staphylococcus aureus were listed as the most frequent pulmonary bacterial groups that colonized COVID-19 patients. In fecal specimens, the numbers of Bacteroidetes, Firmicutes, and Actinobacteria phyla were significantly higher amongst NSCLC patients with COVID-19. NSCLC patients infected with COVID-19 showed lower levels of Lactobacillus spp., Akkermansia muciniphila, and Bifidobacterium spp. The counts of Streptococcus spp., in NSCLC patients with COVID-19 were significantly higher than those of healthy individuals (8.49±0.70 log CFU/g wet feces vs 8.49±0.70 log CFU/g wet feces). Prevotella spp. were enriched in the gut and respiratory tracts of COVID-19 patient groups. The unbiased analysis showed an increment in Enterococcus spp., Streptococcus spp., and Prevotella spp. CONCLUSION: Eventually, it was found that compared to control groups, COVID-19 patients with NSCLC showed diminished gut bacteria diversity and increase in Lactobacillus spp., A. muciniphila, and Bifidobacterium spp. The overgrowth of Enterococcus spp., Streptococcus spp., and Prevotella spp. could be potential predictive biomarkers in the gut-lung axis of NSCLC patients with COVID-19.

The importance of heteroresistance and efflux pumps in bedaquiline-resistant Mycobacterium tuberculosis isolates from Iran.

BACKGROUND: Tuberculosis (TB) continues to pose a threat to communities worldwide and remains a significant public health issue in several countries. We assessed the role of heteroresistance and efflux pumps in bedaquiline (BDQ)-resistant Mycobacterium tuberculosis isolates. METHODS: Nineteen clinical isolates were included in the study, of which fifteen isolates were classified as MDR or XDR, while four isolates were fully susceptible. To evaluate BDQ heteroresistance, the Microplate Alamar Blue Assay (MABA) method was employed. For screening mixed infections, MIRU-VNTR was performed on clinical isolates. Mutations in the atpE and Rv0678 genes were determined based on next-generation sequencing data. Additionally, real-time PCR was applied to assess the expression of efflux pump genes in the absence and presence of verapamil (VP). RESULTS: All 15 drug-resistant isolates displayed resistance to BDQ. Among the 19 total isolates, 21.05% (4/19) exhibited a heteroresistance pattern to BDQ. None of the isolates carried a mutation of the atpE and Rv0678 genes associated with BDQ resistance. Regarding the MIRU-VNTR analysis, most isolates (94.73%) showed the Beijing genotype. Fifteen (78.9%) isolates showed a significant reduction in BDQ MIC after VP treatment. The efflux pump genes of Rv0676c, Rv1258c, Rv1410c, Rv1634, Rv1819, Rv2459, Rv2846, and Rv3065 were overexpressed in the presence of BDQ. CONCLUSIONS: Our results clearly demonstrated the crucial role of heteroresistance and efflux pumps in BDQ resistance. Additionally, we established a direct link between the Rv0676c gene and BDQ resistance. The inclusion of VP significantly reduced the MIC of BDQ in both drug-susceptible and drug-resistant clinical isolates.

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.

Interplay between gut microbiota and the master iron regulator, hepcidin, in the pathogenesis of liver fibrosis.

INTRODUCTION: There is a proven role for hepcidin and the composition of gut microbiota and its derivatives in the pathophysiology of liver fibrosis. AREA COVERED: This review focuses on the literature search regarding the effect of hepcidin and gut microbiota on regulating liver physiology. We presented the regulating mechanisms of hepcidin expression and discussed the possible interaction between gut microbiota and hepcidin regulation. Furthermore, we investigated the importance of the hepcidin gene in biological processes and bacterial interactions using bioinformatics analysis. EXPERT OPINION: One of the main features of liver fibrosis is iron accumulation in hepatic cells, including hepatocytes. This accumulation can induce an oxidative stress response, inflammation, and activation of hepatic stellate cells. Hepcidin is a crucial regulator of iron by targeting ferroportin expressed on hepatocytes, macrophages, and enterocytes. Various stimuli, such as iron load and inflammatory signals, control hepcidin regulation. Furthermore, a bidirectional relationship exists between iron and the composition and metabolic activity of gut microbiota. We explored the potential of gut microbiota to influence hepcidin expression and potentially manage liver fibrosis, as the regulation of iron metabolism plays a crucial role in this context.

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.

Intracerebroventricular Cutibacterium acnes Generates Manifestations of Alzheimer's Disease-like Pathology in the Rat Hippocampus.

The infection hypothesis is a new causative explanation for Alzheimer's disease (AD). In recent decades, various species of bacterial pathogens have been distinguished in the autopsy of Alzheimer's patients; however, the mechanism of bacterial contribution to AD pathology is still unknown. To explore the hypothesis, Cutibacterium acnes (C. acnes) was selected, and effects of its intracerebroventricular (ICV) inoculation in rats was evaluated. The results revealed that C. acnes causes memory impairment, which might be a consequence of upregulated Amyloid ß (Aß) deposits in the hippocampus; Aß aggregates are co-localized with C. acnes colonies. The key point of our hypothesis is that the activation of the innate immune system by C. acnes through the TLR2/NF-κB/NLRP3 signaling pathway, eventually leads to increased neuroinflammation, which might be resulted from microgliosis and astrogliosis. Neuroinflammation increases oxidative stress and cell apoptosis. Overall, the obtained results of this study support our hypothesis that brain exposure to C. acnes prompted neuroinflammation with similar AD-like pathology.

The Effect of Fecal Microbiota Transplantation on Cardiometabolic Risk Factors: A Systematic Review and Meta-Analysis.

PURPOSE: Cardiometabolic disease (CMD) is increasing along with its predisposing factors and adverse consequences. As gut microbiota dysbiosis is established in these patients, fecal microbiota transplantation (FMT), which alters the bacterial composition of the intestine, supposedly can help improve cardiometabolic disturbances. We conducted a systematic review and meta-analysis evaluating the impact of FMT on the cardiometabolic parameters and gut microbiota composition of patients experiencing at least one cardiometabolic issue. METHODS: Eligible studies were searched through the PubMed, Web of Science, and Scopus databases until December 2022. The initial search results underwent duplication removal and screening until each included study was scanned for intended data. The Cochrane risk of bias tool was used to evaluate the methodologic accuracy of studies and the random effects model was used for conducting the meta-analysis. FINDINGS: Eighteen of the original 2414 articles from the literature search were entered into the systematic review; of these, 11 were included in the meta-analysis. Insulin showed a significant decrease by 24.7 pmol/L (weighted mean difference [WMD], -24.77; 95% CI, -48.704 to -0.848) after short-term follow-up, and HDL increased by 0.1 mmol/l(WMD, 0.106; 95% CI, 0.027 to 0.184) and 0.12 mmol/l(WMD, 0.120; 95% CI, 0.003 to 0.237) in those using a capsule deliver mode and in short-term follow-up, respectively. No significant changes were seen in other lipid profiles, blood glucose, insulin resistance, or anthropometric indices. In addition, multiple studies reported gut microbiota alterations after the intervention, including an increase in butyrate-producing species. IMPLICATIONS: Although some articles reported the beneficial effects of FMT on metabolic parameters, we failed to find a clinically significant alteration. Also, information regarding proper donors and the best method to induce FMT have not yet been sufficiently investigated, which should be considered along with means to prevent potential damages. PROSPERO identifier: CRD42022380705.

Effects of hydrolyzed collagen alone or in combination with fish oil on the gut microbiome in patients with major burns.

Burns are associated with gut dysbiosis. Collagen peptides and omega-3 fatty acids (FAs) are suggested to improve wound healing and the inflammatory response. These are also correlated with microbiome colonization. Therefore, the present study aimed to investigate the effect of hydrolyzed collagen alone or in combination with fish oil on specific species of the gut microbiome in patients with major burns. In this randomized double-blind clinical trial, 57 adults (aged 18-60 years) with 20-45% total body surface area burns were randomised into three groups to receive either 40 gr hydrolyzed collagen +10 ml sunflower oil, 40 g hydrolyzed collagen +10 ml fish oil or placebo, divided into two daily drinks, for two weeks. Gut bacteria were measured using the real-time quantitative polymerase chain reaction (qPCR) method. The mean concentration of Bifidobacterium was significantly reduced in the control (P = 0.002) and collagen (P = 0.005) groups compared with the baseline values, whereas no significant change was observed in the collagen omega-3 group. The Firmicutes to Bacteroidetes ratio decreased significantly in the collagen group (p = 0.002) after supplementation compared to baseline . No significant changes in concentration of Lactobacillus, Enterobacteriaceae, and F.prausnitzii were observed between or within the study groups. Two weeks of supplementation with collagen and omega-3 FAs in patients with major burns did not result in a significant difference in the concentration of bacteria measured between the study groups. However, the addition of omega-3 FAs prevented a significant reduction in gut Bifidobacterium. Future studies are suggested to investigate the potential efficacy of these nutrients in improving the gut microbiota and clinical outcomes in major burns. REGISTRATION NUMBER: IRCT20131125015536N9.

The effect of Bacteroides fragilis and its postbiotics on the expression of genes involved in the endocannabinoid system and intestinal epithelial integrity in Caco-2 cells.

Purpose: Gut microbiota and its derivatives by constantly interacting with the host, regulate the host function. Intestinal epithelium integrity is under the control of various factors including the endocannabinoid system (ECS). Accordingly, we aimed at investigating the effect of Bacteroides fragilis and its postbiotics (i.e., heat-inactivated, cell-free supernatants (CFS) and outer membrane vesicles (OMVs)) on the expression of genes involved in ECS (cnr1, faah, pparg) and the epithelial barrier permeability (ocln, tjp1) in a Caco-2 cell line. Methods: Caco-2 cell line was treated with live or heat-inactivated B. fragilis at MOIs of 50 and 100, or stimulated with 7% V/V CFS and B. fragilis OMVs at a dose of 50 and 100 µg/ml overnight. RT-qPCR was applied for expression analysis. Results: Heat-inactivated B. fragilis induced cnr1, pparg, tjp1, and suppressed faah expression, while live B. fragilis had the opposite effect. OMVs increased pparg, and tjp1 expression by reducing the activity of ECS through an increase in faah and a reduction in cnr1 expression. Finally, an increase in the expression of pparg and ocln, and a reduction in the expression of cnr1 was detected in Caco-2 cells treated with CFS. Conclusion: The live and heat-inactivated B. fragilis inversely affected cnr1, faah, pparg, and tjp1 expression in Caco-2 cells. Increased tjp1 mRNA levels by affecting the expression of ECS related genes is taken as an indication of the potential beneficial effects of B. fragilis postbiotics and making them potential candidates for improving permeability in the leaky gut syndrome. Supplementary Information: The online version contains supplementary material available at 10.1007/s40200-023-01264-8.

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.

Simultaneous Genetically Detection of Streptococcuspyogenes, Streptococcuspneumoniae and Haemophilusinfluenzae in Patients with Treatment-Resistant Respiratory Infection.

Background & Objective: Streptococcus pneumoniae, Haemophilus influenzae and Streptococcus pyogenes are among the most important causes of infection in human. Inventing rapid methods to identify these species can help in providing appropriate and effective treatment options. Therefore, the current study aimed to develop a multiplex touch-down PCR method to identify rapidly the aforementioned species patients' sputum samples, simultaneously. Methods: A total of 50 sputum samples of patients with respiratory infections resistant to treatment were collected. After DNA extraction and primer design, the complete capsule (CAP) region II, capsular polysaccharide biosynthesis (cpsA) and the structural regulator of transcription (spy) genes were amplified for detecting H. influenzae, S. pneumoniae and S. pyogenes by multiplex touch-down PCR. Results: Among 50 samples prepared from patients with different diseases, 27 samples were positive for amplified genes. The frequency of presence of pathogens in the collected samples included 14% H. influenzae, 20% S. pneumoniae and 20% S. pyogenes. Also, in some patients, the simultaneous presence of two or three pathogens were observed. Conclusion: In general, it can be concluded that the PCR touchdown method developed in the present study is an effective and fast method for the simultaneous identification of H. influenzae, S. pneumoniae and S. pyogenes pathogens in clinical samples of patients.

The impact of Akkermansia muciniphila and its extracellular vesicles in the regulation of serotonergic gene expression in a small intestine of mice.

OBJECTIVES: A better understanding of host-microbe interactions as a cross-talk between the gastrointestinal (GI) tract and the gut microbiota can help treat and prevent GI disorders by improving the maintenance of GI homeostasis. The gut microbiota can affect signaling molecules, such as serotonin, which regulates endocrine systems through the GI tract. Moreover, studying the effects of gut microbiota in the small intestine on the human GI tract health is pivotal. METHODS: Male C57BL/6J mice (n = 30, 10 mice per group) were orally gavaged with 200 µL of PBS (control group); mice in group II were orally gavaged with 109 colony-forming units (CFU)/200 µL of viable A. muciniphila, suspended in PBS (A. muciniphila group); and mice in group III were orally gavaged with 10 µg of protein/200 µL of EVs (A. muciniphila-EV group) once daily for four weeks. The gene expression of serotonin system-related genes (Slc6a4, Tph1, Mao, Htr3, Htr4, and Htr7) was examined by quantitative real-time PCR (qPCR) method. RESULTS: Based on the results, A. muciniphila significantly affected the mRNA expression of genes related to the serotonin system (Tph1, Mao, Htr3B, and Htr7) in the duodenum and (Htr3B, Htr4 and Htr7) in the ileum of mice (P < 0.05). Moreover, A. muciniphila-derived EVs affected the expression of major genes related to the serotonin system (Tph1, slc6a4a, Mao, Htr3B, Htr4, and Htr7) in the duodenum and ileum of mice (P < 0.05). CONCLUSIONS: The present findings may pave the way for further investigation of the effects of strain-specific probiotics on the serotonergic system, which is currently in its infancy.

Characterization of gut microbiota profile in Iranian patients with bipolar disorder compared to healthy controls.

Introduction: The human gut microbiota plays a crucial role in mental health through the gut-brain axis, impacting central nervous system functions, behavior, mood, and anxiety. Consequently, it is implicated in the development of neuropsychiatric disorders. This study aimed to assess and compare the gut microbiota profiles and populations of individuals with bipolar disorder and healthy individuals in Iran. Methods: Fecal samples were collected from 60 participants, including 30 bipolar patients (BPs) and 30 healthy controls (HCs), following rigorous entry criteria. Real-time quantitative PCR was utilized to evaluate the abundance of 10 bacterial genera/species and five bacterial phyla. Results: Notably, Actinobacteria and Lactobacillus exhibited the greatest fold change in BPs compared to HCs at the phylum and genus level, respectively, among the bacteria with significant population differences. Ruminococcus emerged as the most abundant genus in both groups, while Proteobacteria and Bacteroidetes showed the highest abundance in BPs and HCs, respectively, at the phylum level. Importantly, our investigation revealed a lower Firmicutes/Bacteroidetes ratio, potentially serving as a health indicator, in HCs compared to BPs. Conclusion: This study marks the first examination of an Iranian population and provides compelling evidence of significant differences in gut microbiota composition between BPs and HCs, suggesting a potential link between brain functions and the gut microbial profile and population.

Tuberculosis prevention, diagnosis, and treatment financial profile during 2006-2021: PART A.

BACKGROUND: Tuberculosis (TB) is a communicable disease that is a major cause of death and one of the leading causes of death worldwide. Currently, there is no analyzed data to examine the financial profile of TB by country, continent, and year; this article analyzed TB prevention, diagnosis, and treatment financial profile during the last two decades. METHODS: Original research, reviews, and governmental databases are analyzed to present the financial profile of TB. RESULTS: Analyzed data showed Europe (23137.133), Asia (20137.073), and Africa (15237.973) had the most allocated funds (US $ million), and Oceania (236.702), and America (4745.043) had the lowest allocated fund (US $ million) during 2006-2021. Additionally, the allocation of funds (domestic funds, global funds, and grants [excluding global funds]) in different countries and proper planning for TB eradication has caused that in the last two decades, the slope of the confirmed cases and deaths graph line is negative. CONCLUSION: The number of confirmed cases and deaths reported globally is decreasing. The trend lines showed that the assigned funds are increasing, indicating that the TB eradication plan can be apprehended soon.

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.