The Gut Microbiota and Major Depressive Disorder: Current Understanding and Novel Therapeutic Strategies.

Major depressive disorder (MDD) is a common neuropsychiatric challenge that primarily targets young females. MDD as a global disorder has a multifactorial etiology related to the environment and genetic background. A balanced gut microbiota is one of the most important environmental factors involved in human physiological health. The interaction of gut microbiota components and metabolic products with the hypothalamic-pituitary-adrenal system and immune mediators can reverse depression phenotypes in vulnerable individuals. Therefore, abnormalities in the quantitative and qualitative structure of the gut microbiota may lead to the progression of MDD. In this review, we have presented an overview of the bidirectional relationship between gut microbiota and MDD, and the effect of pre-treatments and microbiomebased approaches, such as probiotics, prebiotics, synbiotics, fecal microbiota transplantation, and a new generation of microbial alternatives, on the improvement of unstable clinical conditions caused by MDD.

Gut Microbiota Composition in Patients with Neurodegenerative Disorders (Parkinson's and Alzheimer's) and Healthy Controls: A Systematic Review.

This systematic review aims to provide a comprehensive understanding of the current literature regarding gut microbiota composition in patients with Parkinson's disease (PD) and Alzheimer's disease (AD) compared to healthy controls. To identify the relevant studies, a thorough search of PubMed, Medline, and Embase was conducted following the PRISMA guidelines. Out of 5627 articles, 73 studies were assessed for full-text eligibility, which led to the inclusion of 42 studies (26 PD and 16 AD studies). The risk of bias assessment showed a medium risk in 32 studies (20 PD studies and 12 AD studies), a low risk in 9 studies (5 PD studies and 4 AD studies), and 1 PD study with a high risk. Among the PD studies, 22 out of 26 studies reported a different gut microbiota composition between the PD cases and the healthy controls, and 15 out of 16 AD studies reported differences in gut microbiota composition between the AD cases and the healthy controls. The PD and AD studies consistently identified the phyla Bacteroidetes, Firmicutes, and Proteobacteria as prevalent in the gut microbiota in both the healthy groups and the case groups. Microbial dysbiosis was specifically characterized in the PD studies by a high abundance of Akkermansia, Verrucomicrobiaceae, Lachnospiraceae, and Ruminococcaceae in the cases and a high abundance of Blautia, Coprococcus, Prevotellaceae, and Roseburia in the controls. Similarly, Bacteroides and Acidobacteriota were abundant in the AD cases, and Acidaminococcaceae, Firmicutes, Lachnospiraceae, and Ruminiclostridium were abundant in the AD controls. The microbial signature assessment showed the association of several microbial taxa, including Akkermansia, Lachnospiraceae, Verrucomicrobiaceae, Bifidobacterium, Ruminococcacea, and Verrucomicrobia with PD and Ruminococcaceae, Bacteroides, and Actinobacteria with AD. The microbial diversity evaluations in the PD and AD studies indicated comparable alpha diversity in some groups and distinct gut microbiota composition in others, with consistent beta diversity differences between the cases and the controls across multiple studies. The bacterial signatures identified in this study that are associated with PD and AD may offer promising prospects for efficient management and treatment approaches.

The gut microbiota and celiac disease: Pathophysiology, current perspective and new therapeutic approaches.

Celiac disease (CD) as a chronic gluten-sensitive intestinal condition, mainly affects genetically susceptible hosts. The primary determinants of CD have been identified as environmental and genetic variables. The development of CD is significantly influenced by environmental factors, including the gut microbiome. Therefore, gut microbiome re-programming-based therapies using probiotics, prebiotics, postbiotics, gluten-free diet, and fecal microbiota transplantation have shown promising results in the modification of the gut microbiome. Due to the importance and paucity of information regarding the CD pathophysiology, in this review, we have covered the association between CD development and gut microbiota, the effects of infectious agents, particularly the recent Covid-19 infection in CD patients, and the efficacy of potential therapeutic approaches in the CD have been discussed. Hence, scientific literature indicates that the diverse biological functions of the gut microbiota against immunomodulatory responses have made microbiome-based therapy an alternative therapeutic paradigm to ameliorate the symptoms of CD and quality of life. However, the exact potential of microbiota-based techniques that aims to quantitatively and qualitatively alter the gut microbiota to be used in the treatment and ameliorate the symptoms of CD will be determined with further research in the future.

Evaluation of Helicobacter pylori Genotypes in Obese Patients with Gastric Ulcer, Duodenal Ulcer, and Gastric Cancer: An Observational Study.

INTRODUCTION: Obesity is a well-known risk factor for a variety of gastrointestinal disorders (GID). Helicobacter pylori is associated with different GID, such as gastric cancer and chronic gastritis. In this study, we investigated the prevalence of dominant genotypes in H. pylori isolated from obese patients diagnosed with gastric ulcer, duodenal ulcer, and gastric cancer. METHODS: A total of 222 H. pylori-positive samples were collected from patients with obesity. GID and gastric cancer were identified by endoscopy and histopathology, respectively. Three biopsy specimens from the gastric antrum were obtained from each patient for culture tests, histological examination, and identification of vacuolating cytotoxin A (vacA) (vacA s1, vacA s2, vacA m1, vacA m2, vacA s1m1 vacA s1m2, vacA s2m1, and vacA s2m2), cagA, cagE, iceA1, oipA, dupA, and babA2 using polymerase chain reaction. RESULTS: vacA, cagE, cagA, iceA1, oipA, dupA, and babA2 genes were detected in 222 (100%), 171 (77%), 161 (72.5%), 77 (34.6%), 77 (34.6%), 137 (61%), and 69 (31%) patients with obesity, respectively. Our findings revealed that vacA, iceA1, oipA, and babA2 were significantly associated with a higher risk of GID, while cagE, cagA, and dupA indicated no correlation with the development of GID. Also, in the combination of s- and m-region genotypes, s1m2 (79%) was the most frequently identified genotype in patients with obesity. A significant association was also found between cagA and the presence of vacA genotypes (except for vacA m1 and babA2). CONCLUSIONS: This study indicated the high prevalence of different virulence genes in H. pylori isolated from obese patients and supported the significant role of H. pylori in the development of GID.

Identification and characterization of the type II toxin-antitoxin systems in the carbapenem-resistant Acinetobacterbaumannii.

Carbapenem -resistant A. baumannii (CRAB) is a major cause of both community-associated and nosocomial infections that are difficult to control and treat worldwide. Among different mediators of pathogenesis, toxin-antitoxin (TA) systems are emerging as the most prominent. The functional diversity and ubiquitous distribution in bacterial genomes are causing significant attention toward TA systems in bacteria. However, there is no enough information on the prevalence and identity of TA systems in CRAB clinical isolates. This study aimed to identify type II toxin-antitoxin systems in carbapenem-resistant A. baumannii (CRAB) isolates. A total of 80 A. baumannii isolates were collected from different clinical samples. Antibiotic resistance patterns of A. baumannii isolates were evaluated phenotypically and genetically. The frequency of type II TA genes was evaluated in CRAB isolates using PCR. Moreover, the expression level of the most prevalent TA encoding genes in some clinical isolates were evaluated by RT-qPCR. To determine whether the SplT and SplA are functional, the growth of E. coli BL21 cells (DE3/pLysS) harboring pET28a, pET28a-splTA, and pET28a-splT were analyzed by kill-rescue assay. All of the isolates were resistant to third generation of cephalosporins, ciprofloxacin and levofloxacin, whereas, 72%, 81% and 87% were resistant to amikacin, carbapenems and tetracycline, respectively. The cheTA in 47 isolates (72.5%) and splTA in 39 isolates (60%) of 65 isolates were the most common genes encoding type II TA among CRAB isolates. RT-qPCR demonstrated that cheTA and splTA transcripts are produced in the clinical isolates. There was a significant correlation between the presence of splTA genes and blaOXA-24 in CRAB isolates. Over-expression of the splT gene in E. coli results in inhibition of bacterial growth, whereas co-expression of splTA effectively restores the growth. This study presents the first identification of the type II TA systems among the carbapenem -resistant A. baumannii isolates, in Iran.

Evaluation of Host Immune Response in Diabetic Foot Infection Tissues Using an RNA Sequencing-Based Approach.

The normal continuity of skin tissue can be affected by invading pathogens and lead to a series of complicated physiological events. Using an RNA sequencing-based approach, we have captured a metatranscriptomic landscape from diabetic foot infections (DFIs). The hierarchical clustering of the top 2,000 genes showed the expression of four main clusters in DFIs (A, B, C, and D). Clusters A and D were enriched in genes mainly involved in the recruitment of inflammatory cells and immune responses and clusters B and C were enriched in genes related to skin cell development and wound healing processes such as extracellular structure organization and blood vessel development. Differential expression analysis showed more than 500 differentially expressed genes (DEGs) between samples with a low number of virulence factors and samples with a high number of virulence factors. Up-regulated and down-regulated genes were mainly involved in adaptive/native immune responses and transport of mature mRNAs, respectively. Our results demonstrated the importance of inflammatory cytokines of adaptive/native immunity in the progression of DFIs and provided a useful groundwork for capturing gene snapshots in DFIs. In addition, we have provided a general introduction to the challenges and opportunities of RNA sequencing technology in the evaluation of DFIs. Pathways identified in this study such as immune chemokines, Rho GTPases, and corresponding effectors might be important therapeutic targets in the management of DFIs.

Metatranscriptomic Analysis Reveals Active Bacterial Communities in Diabetic Foot Infections.

Despite the extended view of the composition of diabetic foot infections (DFIs), little is known about which transcriptionally active bacterial communities are pertinent to infection, and if any differences are associated with increased infection severity. We applied a RNA sequencing approach to analyze the composition, function, and pathogenicity of the active bacterial communities in DFIs. Taxonomic profiling of bacterial transcripts revealed the presence of 14 bacterial phyla in DFIs. The abundance of the Spiroplasma, Vibrio, and Mycoplasma were significantly different in different infection severities (P < 0.05). Mild and severe stages of infections were dominated by Staphylococcus aureus and Porphyromonas asaccharolytica, respectively. A total of 132 metabolic pathways were identified of which ribosome and thiamin being among the most highly transcribed pathways. Moreover, a total of 131 antibiotic resistance genes, primarily involved in the multidrug efflux pumps/exporters, were identified. Furthermore, iron acquisition systems (synthesize and regulation of siderophores) and pathways involved in the synthesis and regulation of cell-surface components associated with adhesion, colonization, and movement of bacterial cells were the most common virulence factors. These virulence factors may help bacteria compete for scares resources and survive the host wound proteases. Characterization of transcriptionally active bacterial communities can help to provide an understanding of the role of key pathogens in the development of DFIs. Such information can be clinically useful allowing replacement of DFIs empirical therapy with targeted treatment.

Management of antibiotic-resistant Helicobacter pylori infection: current perspective in Iran.

Helicobacter pylori is a common gastric bacterial pathogen implicated in the pathogenesis of many digestive tract disorders. H. pylori infection prevalence has been reported alarmingly in Iran. A plethora of studies have been conducted to evaluate the efficiency of first-line and second-line eradication attempts in patients diagnosed with H. pylori infections in Iran. The present study, was evaluated the efficacy of first-line and second-line therapy in H. pylori infections in Iran. We aimed to consider the literature review of the various library and electronic databases (Science Direct, PubMed, and Google Scholar) until 2020. The frequency of bacterial resistance to tetracycline, ampicillin, trimethoprim, erythromycin, ofloxacin, and metronidazolewas found to be high in Iran, while the most effective antibiotics were clarithromycin, rifampin, rifampicin, tetracycline, amoxicillin, ciprofloxacin, levofloxacin, moxifloxacin, and azithromycin. The therapeutic choice for H. pylori eradication in Iran could be quadruple therapy using two antibiotics amoxicillin and metronidazole/clarithromycin for the first-line regimen, and a combination of furazolidone plus tetracycline/amoxicillin and bismuth plus proton pump inhibitor for the second-line regimen. Due to increased antibiotic resistance in our region, empirical therapy must be replaced by more targeted treatment based on antimicrobial drug resistance profiles obtained from patients. Although we limited our investigation on the H. pylori eradication regimens in Iran, the results can be generalized to any region as long as the patterns of resistance are the same.

Host DNA depletion efficiency of microbiome DNA enrichment methods in infected tissue samples.

Shotgun metagenomic sequencing or metagenomic whole genome sequencing is a genome-wide sequencing approach to explore bacterial communities directly from their habitat or sites of infection. However, host DNA contamination in metagenomic sequencing overwhelm low biomass of microbial signals and decrease sensitivity for microbial detection. In this study, we evaluated the host DNA depletion efficiency of four different microbiome DNA enrichment methods (NEBNext Microbiome DNA Enrichment kit, Molzym Ultra-Deep Microbiome Prep, QIAamp DNA Microbiome kit and Zymo HostZERO microbial DNA kit) in diabetic foot infection (DFI) tissue samples using quantitative real-time PCR and their effect on bacterial community composition by 16S ribosomal RNA amplicon sequencing. The host DNA depletion ratio (18S/16S rRNA), the percentage of bacterial DNA component and the microbial community profile of DFI were compared before (control) and after each microbiome DNA enrichment method. There was a significant difference in the 18S/16S rRNA ratio among different microbiome DNA enrichment methods (p <.001). QIAamp and HostZERO method reduced 18S/16S rRNA ratio by 32 and 57 fold than control method respectively. The percentage of bacterial DNA component increased more than ten-fold in QiaAmp (71.0 ± 2.7%) and HostZERO (79.9 ± 3.1%) method respectively than those in control method without host DNA depletion (6.7 ± 0.1%). It demonstrated the host DNA contamination was efficiently depleted and bacterial DNA was effectively enriched in HostZERO and QIAamp methods, attesting to the efficacy of these two methods in shotgun metagenomic sequencing studies. Overall, bacterial community composition of DFI samples was similar between control and microbiome enriched DNA samples.

Specification of Bacteriophage Isolated Against Clinical Methicillin-Resistant Staphylococcus Aureus.

OBJECTIVES: The emergence of resistant bacteria is being increasingly reported around the world, potentially threatening millions of lives. Amongst resistant bacteria, methicillin-resistant Staphylococcus aureus (MRSA) is the most challenging to treat. This is due to emergent MRSA strains and less effective traditional antibiotic therapies to Staphylococcal infections. The use of bacteriophages (phages) against MRSA is a new, potential alternate therapy. In this study, morphology, genetic and protein structure of lytic phages against MRSA have been analysed. METHODS: Isolation of livestock and sewage bacteriophages were performed using 0.4 µm membrane filters. Plaque assays were used to determine phage quantification by double layer agar method. Pure plaques were then amplified for further characterization. Sulfate-polyacrylamide gel electrophoresis and random amplification of polymorphic DNA were run for protein evaluation, and genotyping respectively. Transmission electron microscope was also used to detect the structure and taxonomic classification of phage visually. RESULTS: Head and tail morphology of bacteriophages against MRSA were identified by transmission electron microscopy and assigned to the Siphoviridae family and the Caudovirales order. CONCLUSION: Bacteriophages are the most abundant microorganism on Earth and coexist with the bacterial population. They can destroy bacterial cells successfully and effectively. They cannot enter mammalian cells which saves the eukaryotic cells from lytic phage activity. In conclusion, phage therapy may have many potential applications in microbiology and human medicine with no side effect on eukaryotic cells.