In Vitro Influence of Specific Bacteroidales Strains on Gut and Liver Health Related to Metabolic Dysfunction-Associated Fatty Liver Disease.

Metabolic dysfunction-associated fatty liver disease (MAFLD) has become a major health risk and a serious worldwide issue. MAFLD typically arises from aberrant lipid metabolism, insulin resistance, oxidative stress, and inflammation. However, subjacent causes are multifactorial. The gut has been proposed as a major factor in health and disease, and over the last decade, bacterial strains with potentially beneficial effects on the host have been identified. In vitro cell models have been commonly used as an early step before in vivo drug assessment and can confer complementary advantages in gut and liver health research. In this study, several selected strains of the order Bacteroidales were used in a three-cell line in vitro analysis (HT-29, Caco-2, and HepG2 cell lines) to investigate their potential as new-generation probiotics and microbiota therapeutics. Antimicrobial activity, a potentially useful trait, was studied, and the results showed that Bacteroidales can be a source of either wide- or narrow-spectrum antimicrobials targeting other closely related strains. Moreover, Bacteroides sp. 4_1_36 induced a significant decrease in gut permeability, as evidenced by the high TEER values in the Caco-2 monolayer assay, as well as a reduction in free fatty acid accumulation and improved fatty acid clearance in a steatosis HepG2 model. These results suggest that Bacteroidales may spearhead the next generation of probiotics to prevent or diminish MAFLD.

Impact of the COVID-19 Pandemic on the Epidemiological Situation of Pulmonary Tuberculosis-Using Natural Language Processing.

BACKGROUND: We aimed to analyze the impact of the COVID-19 pandemic on pulmonary tuberculosis (TB) using artificial intelligence. To do so, we compared the real-life situation during the pandemic with the pre-2020 situation. METHODS: This non-interventional, retrospective, observational study applied natural language processing to the electronic health records of the Castilla-La Mancha region of Spain. The analysis was conducted from January 2015 to December 2020. RESULTS: A total of 2592 patients were diagnosed with pulmonary tuberculosis; 64.6% were males, and the mean age was 53.5 years (95%CI 53.0-54.0). In 2020, pulmonary tuberculosis diagnoses dropped by 28% compared to 2019. In total, 62 (14.2%) patients were diagnosed with COVID-19 and pulmonary tuberculosis coinfection in 2020, with a mean age of 52.3 years (95%CI 48.3-56.2). The main symptoms in these patients were dyspnea (27.4%) and cough (35.5%), although their comorbidities were no greater than patients with isolated TB. The female sex was more frequently affected, representing 53.4% of this patient subgroup. CONCLUSIONS: During the first year of the COVID-19 pandemic, a decrease was observed in the incidence of pulmonary tuberculosis. Women presented a significantly higher risk for pulmonary tuberculosis and COVID-19 coinfection, although the symptoms were not more severe than patients diagnosed with pulmonary tuberculosis alone.

The Clinical Profile of Patients with COPD Is Conditioned by Age.

In recent years, many studies have analyzed the importance of integrating time, or aging, into the equation that relates genetics and the environment to the development and origin of COPD. Under conditions of daily clinical practice, our study attempts to identify the differences in the clinical profile of patients with COPD according to age and the impact on the global burden of the disease. This study is non-interventional and observational, using artificial intelligence and data captured from electronic medical records. The study population included patients who were diagnosed with COPD between 2011 and 2021. A total of 73,901 patients had a diagnosis of COPD. The mean age was 73 years (95% CI: 72.9-73.1), and 56,763 were men (76.8%). We observed a specific prevalence of obesity, heart failure, depression, and hiatal hernia in women (p < 0.001), and ischemic heart disease and obstructive sleep apnea (OSA) in men (p < 0.001). In the analysis by age ranges, a progressive increase in cardiovascular risk factors was observed with age. In conclusion, in a real-life setting, COPD is a disease that primarily affects older subjects and frequently presents with comorbidities that are decisive in the evolutionary course of the disease.

Chronic Respiratory Diseases as a Risk Factor for Herpes Zoster Infection.

INTRODUCTION: Herpes zoster (HZ) is a condition that results from the reactivation of the varicella zoster virus (VZV). Several diseases have been reported to increase the risk of developing HZ and postherpetic neuralgia (PHN). The objective of this study is to analyze the prevalence and risk factors for HZ and PHN in the most frequent chronic respiratory diseases, which are chronic obstructive pulmonary disease (COPD), asthma, lung cancer and obstructive sleep apnea (OSA). METHODS: We conducted an observational, retrospective, non-interventional study between January 2012 and December 2020 based on data from the Castilla-La Mancha Regional Health System in Spain. We used the Savana Manager 3.0 artificial intelligence-enabled system to collect information from electronic medical records. RESULTS: 31765 subjects presented a diagnosis of HZ. Mean age was 64.5 years (95%CI 64.3-64.7), and 58.2% were women. The prevalence of HZ showed an increasing trend in patients over the age of 50. A risk analysis adjusted for sex and comorbidities in COPD, asthma, lung cancer and OSA presented a higher risk of developing HZ in the first three (OR 1.16 [95%CI 1.13-1.19], 1.67 [1.63-1.71], 1.68 [1.60-1.76], respectively), which further increased in all three when associated with comorbidities. Regarding postherpetic neuralgia, an increased risk was only observed related to COPD and lung cancer (OR 1.24 [95%CI 1.23-1.25], 1.14 [1.13-1.16], respectively), further increasing when associated with comorbidities. CONCLUSIONS: In a standard clinical practice setting, the most prevalent respiratory diseases (asthma, COPD and lung cancer) are related to a higher risk of HZ and PHN. These data are fundamental to assess the potential impact of vaccination in this population.

Bioinformatic mining for RiPP biosynthetic gene clusters in Bacteroidales reveals possible new subfamily architectures and novel natural products.

The Bacteroidales order, widely distributed among diverse human populations, constitutes a key component of the human microbiota. Members of this Gram-negative order have been shown to modulate the host immune system, play a fundamental role in the gut's microbial food webs, or be involved in pathogenesis. Bacteria inhabiting such a complex environment as the human microbiome are expected to display social behaviors and, hence, possess factors that mediate cooperative and competitive interactions. Different types of molecules can mediate interference competition, including non-ribosomal peptides (NRPs), polyketides, and bacteriocins. The present study investigates the potential of Bacteroidales bacteria to biosynthesize class I bacteriocins, which are ribosomally synthesized and post-translationally modified peptides (RiPPs). For this purpose, 1,136 genome-sequenced strains from this order were mined using BAGEL4. A total of 1,340 areas of interest (AOIs) were detected. The most commonly identified enzymes involved in RiPP biosynthesis were radical S-adenosylmethionine (rSAM), either alone or in combination with other biosynthetic enzymes such as YcaO. A more comprehensive analysis of a subset of 9 biosynthetic gene clusters (BGCs) revealed a consistent association in Bacteroidales BGCs between peptidase-containing ATP-binding transporters (PCATs) and precursor peptides with GG-motifs. This finding suggests a possibly shared mechanism for leader peptide cleavage and transport of mature products. Notably, human metagenomic studies showed a high prevalence and abundance of the RiPP BGCs from Phocaeicola vulgatus and Porphyromonas gulae. The mature product of P. gulae BGC is hypothesized to display γ-thioether linkages and a C-terminal backbone amidine, a potential new combination of post-translational modifications (PTM). All these findings highlight the RiPP biosynthetic potential of Bacteroidales bacteria, as a rich source of novel peptide structures of possible relevance in the human microbiome context.

Clinical Profile of Patients with Idiopathic Pulmonary Fibrosis in Real Life.

OBJECTIVE: The objective of this study is to define the real-life clinical profile and therapeutic management of patients with idiopathic pulmonary fibrosis using artificial intelligence. METHODS: We have conducted an observational, retrospective, non-interventional study using data from the Castilla-La Mancha Regional Healthcare Service (SESCAM) in Spain between January 2012 and December 2020. The Savana Manager 3.0 artificial intelligence platform was used to collect information from electronic medical records by applying natural language processing. RESULTS: Our study includes 897 subjects whose diagnosis was compatible with idiopathic pulmonary fibrosis; 64.8% were men, with a mean age of 72.9 years (95% CI 71.9-73.8), and 35.2% were women, with a mean age of 76.8 years (95% CI 75.5-78). Patients who had a family history of IPF (98 patients; 12%) were younger and predominantly female (53.1%). Regarding treatment, 45% of patients received antifibrotic therapy. Patients who had undergone lung biopsy, chest CT, or bronchoscopy were younger than the patient population in whom these studies were not completed. CONCLUSIONS: This study has used artificial intelligence techniques to analyze a large population over a 9-year period and determine the situation of IPF in standard clinical practice by identifying the patient clinical profile, use of diagnostic tests and therapeutic management.

Role of microbiota and related metabolites in gastrointestinal tract barrier function in NAFLD.

The Gastrointestinal (GI) tract is composed of four main barriers: microbiological, chemical, physical and immunological. These barriers play important roles in maintaining GI tract homeostasis. In the crosstalk between these barriers, microbiota and related metabolites have been shown to influence GI tract barrier integrity, and alterations of the gut microbiome might lead to an increase in intestinal permeability. As a consequence, translocation of bacteria and their products into the circulatory system increases, reaching proximal and distal tissues, such as the liver. One of the most prevalent chronic liver diseases, Nonalcoholic Fatty Liver Disease (NAFLD), has been associated with an altered gut microbiota and barrier integrity. However, the causal link between them has not been fully elucidated yet. In this review, we aim to highlight relevant bacterial taxa and their related metabolites affecting the GI tract barriers in the context of NAFLD, discussing their implications in gut homeostasis and in disease.

Clinical Management of COPD in a Real-World Setting. A Big Data Analysis. / Manejo clínico de la EPOC en situación de vida real. Análisis a partir de big data.

OBJECTIVE: The aim of this study was to evaluate the quality of diagnosis and treatment of COPD using Big Data methodology on the Savana Manager 2.1 clinical platform. MATERIALS AND METHODS: A total of 59,369 patients with a diagnosis of COPD were included from a population of 1,219,749 adults over 40 years of age. RESULTS: In total, 78% were men. Spirometry data were available for only 26,453 (43.5%) subjects. Disease severity was classified in 18,172 patients: 4,396 mild, 7,100 moderate, and 6,676 severe, although only 27%, 34%, and 28%, respectively, presented obstructive spirometry. The clinical management of COPD is mainly the responsibility of the primary care and pulmonology departments, while internal medicine and, to a lesser extent, geriatrics also participate. Drug treatment was based on bronchodilators and inhaled corticosteroids (ICS). A marked decline in the use of long-acting beta-2 agonists (LABA) in monotherapy and a slight reduction in ICS/LABA combinations, associated with a LAMA in 74% of cases, was observed. All-cause in-hospital mortality among the overall population was 5.6% compared to 1% of the general population older than 40 years. In total, 35% were admitted to hospital, with an average stay of 6.6 days and a rate of hospital mortality in this group of 10.74%. DISCUSSION: This study identifies the main features of an unselected COPD population and the major errors made in the management of the disease.

Characteristics and Prognosis of COVID-19 in Patients with COPD.

Patients with Chronic Obstructive Pulmonary Disease (COPD) have a higher prevalence of coronary ischemia and other factors that put them at risk for COVID-19-related complications. We aimed to explore the impact of COVID-19 in a large population-based sample of patients with COPD in Castilla-La Mancha, Spain. We analyzed clinical data in electronic health records from 1 January to 10 May 2020 by using Natural Language Processing through the SAVANA Manager® clinical platform. Out of 31,633 COPD patients, 793 had a diagnosis of COVID-19. The proportion of patients with COVID-19 in the COPD population (2.51%; 95% CI 2.33-2.68) was significantly higher than in the general population aged >40 years (1.16%; 95% CI 1.14-1.18); p < 0.001. Compared with COPD-free individuals, COPD patients with COVID-19 showed significantly poorer disease prognosis, as evaluated by hospitalizations (31.1% vs. 39.8%: OR 1.57; 95% CI 1.14-1.18) and mortality (3.4% vs. 9.3%: OR 2.93; 95% CI 2.27-3.79). Patients with COPD and COVID-19 were significantly older (75 vs. 66 years), predominantly male (83% vs. 17%), smoked more frequently, and had more comorbidities than their non-COPD counterparts. Pneumonia was the most common diagnosis among COPD patients hospitalized due to COVID-19 (59%); 19% of patients showed pulmonary infiltrates suggestive of pneumonia and heart failure. Mortality in COPD patients with COVID-19 was associated with older age and prevalence of heart failure (p < 0.05). COPD patients with COVID-19 showed higher rates of hospitalization and mortality, mainly associated with pneumonia. This clinical profile is different from exacerbations caused by other respiratory viruses in the winter season.

Combining Modules for Versatile and Optimal Labeling of Lactic Acid Bacteria: Two pMV158-Family Promiscuous Replicons, a Pneumococcal System for Constitutive or Inducible Gene Expression, and Two Fluorescent Proteins.

Labeling of bacterial cells with fluorescent proteins allows tracking the bacteria in competition and interactomic in vivo and in vitro studies. During the last years, a few plasmid vectors have been developed aimed at the fluorescent labeling of specific members of the lactic acid bacteria (LAB), a heterogeneous group that includes microorganisms used in the food industry, as probiotics, or as live vectors for mucosal vaccines. Successful and versatile labeling of a broad range of LAB not only requires a vector containing a promiscuous replicon and a widely recognized expression system for the constitutive or regulated expression of the fluorescence determinant, but also the knowledge of the main features of the entire plasmid/host/fluorescent protein ensemble. By using the LAB model species Lactococcus lactis, we have compared the utility properties of a set of labeling vectors constructed by combining a promiscuous replicon (pMV158 or pSH71) of the pMV158 plasmid family with the gene encoding either the EGFP or the mCherry fluorescent protein placed under control of promoter PX or PM from the pneumococcal mal gene cluster for maltosaccharide uptake and utilization, respectively. Some vectors carrying PM also harbor the malR gene, whose product represses transcription from this promoter, thus enabling maltose-inducible synthesis of the fluorescent proteins. We have determined the plasmid copy number (PCN) and segregational stability of the different constructs, as well as the effect of these features on the fitness and fluorescence intensity of the lactococcal host. Constructs based on the pSH71 replicon had a high copy number (∼115) and were segregationally stable. The copy number of vectors based on the pMV158 replicon was lower (∼8-45) and varied substantially depending on the genetic context of the plasmid and on the bacterial growth conditions; as a consequence, inheritance of these vectors was less stable. Synthesis of the fluorescent proteins encoded by these plasmids did not significantly decrease the host fitness. By employing inducible expression vectors, the fluorescent proteins were shown to be very stable in this bacterium. Importantly, conditions for accurate quantification of the emitted fluorescence were established based on the maturation times of the fluorescent proteins.