A catalogue of 1,167 genomes from the human gut archaeome

The human gut microbiome plays an important role in health, but its archaeal diversity remains largely unexplored. In the present study, we report the analysis of 1,167 nonredundant archaeal genomes (608 high-quality genomes) recovered from human gastrointestinal tract, sampled across 24 countries and rural and urban populations. We identified previously undescribed taxa including 3 genera, 15 species and 52 strains. Based on distinct genomic features, we justify the split of the Methanobrevibacter smithii clade into two separate species, with one represented by the previously undescribed ‘CandidatusMethanobrevibacter intestini’. Patterns derived from 28,581 protein clusters showed significant associations with sociodemographic characteristics such as age groups and lifestyle. We additionally show that archaea are characterized by specific genomic and functional adaptations to the host and carry a complex virome. Our work expands our current understanding of the human archaeome and provides a large genome catalogue for future analyses to decipher its impact on human physiology.

The Advantages and Disadvantages of Prokinetics

Prokinetics are medications that enhance gastrointestinal contractility; they improve the symptoms of patients with delayed gastrointestinal motility. Prokinetics have conventionally been used to stimulate gastrointestinal propulsion and to treat symptoms correlated with motility problems, including gastroparesis and constipation. 5-Hydroxytryptamine receptor 4 (5-HT4) agonists, such as cisapride, very effectively increased human gastrointestinal tract motility. However, cisapride sometimes induced serious tachyarrhythmia; the drug was thus withdrawn from the market. Thereafter, many prokinetics have been developed to treat delayed gastrointestinal motility. However, some exhibit serious side-effects. Recently, a new, highly selective serotonin receptor agonist, prucalopride, has been introduced; there is as yet no evidence of serious cardiac side- effects. The drug has been approved by the Food and Drug Administration to treat chronic constipation. Thus, recently introduced, highly selective agents appear to show promise as treatments for gastrointestinal dysmotility; there seem to be no serious side-effects.

Prevalence, Risk Factors, and Molecular Epidemiology of Intestinal Carbapenem-Resistant Pseudomonas aeruginosa

Pseudomonas aeruginosa may become multidrug-resistant (MDR) due to multiple inherited and acquired resistance mechanisms. The human gastrointestinal tract is known as a reservoir of P. aeruginosa and its resistance genes.

Sarecycline exhibits decreased activity Against Representative Bacterial and Fungal Microflora Commonly Present in the Human Gastrointestinal Tract

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Xylan utilisation promotes adaptation of Bifidobacterium pseudocatenulatum to the human gastrointestinal tract

Dietary carbohydrates impact the composition of the human gut microbiota. However, the relationship between carbohydrate availability for individual bacteria and their growth in the intestinal environment remains unclear. Here, we show that the availability of long-chain xylans (LCX), one of the most abundant dietary fibres in the human diet, promotes the growth of Bifidobacterium pseudocatenulatum in the adult human gut. Genomic and phenotypic analyses revealed that the availability of LCX-derived oligosaccharides is a fundamental feature of B. pseudocatenulatum, and that some but not all strains possessing the endo-1,4-β-xylanase (BpXyn10A) gene grow on LCX by cleaving the xylose backbone. The BpXyn10A gene, likely acquired by horizontal transfer, was incorporated into the gene cluster for LCX-derived oligosaccharide utilisation. Co-culturing with xylanolytic Bacteroides spp. demonstrated that LCX-utilising strains are more competitive than LCX non-utilising strains even when LCX-derived oligosaccharides were supplied. In LCX-rich dietary interventions in adult humans, levels of endogenous B. pseudocatenulatum increased only when BpXyn10A was detected, indicating that LCX availability is a fitness determinant in the human gut. Our findings highlight the enhanced intestinal adaptability of bifidobacteria via polysaccharide utilisation, and provide a cornerstone for systematic manipulation of the intestinal microbiota through dietary intervention using key enzymes that degrade polysaccharide as biomarkers.

Evaluation and characterisation of candidate prebiotics extracted from coconut husk by ultrasound-assisted extraction technique

Oligosaccharides are carbohydrates containing between three to ten sugar moieties. Certain oligosaccharides such as inulin and fructo-oligosaccharides are known as prebiotics that promote the growth of beneficial bacteria in the human gastrointestinal tract. This study began by comparing the efficiency of two different solvents (distilled water and 10% w/v sodium hydroxide) in extracting oligosaccharides from the coconut husk by ultrasound-assisted extraction (UAE). Following that, the coconut husk extract (CHE) extract was subjected to a series of prebiotic evaluation tests. The findings indicated that a significantly high extraction yield (40.51 ± 6.00%) could be achieved with 10% w/v NaOH treatment. The in vitro enzymatic digestion study found that there was 43.70 ± 0.15% of hydrolysis at pH 8 after five hours of incubation. For the in vitro gastric juice digestion, 29.21 ± 0.71% of hydrolysis was recorded at pH 1 after four hours of incubation. The extract was able to stimulate the growth of selected beneficial bacterial strains. FTIR and NMR analysis of the CHE revealed that the extract has a similar structure to the well-known prebiotic inulin.

ANALYSIS OF TISSUE EOSINOPHILS IN THE STRUCTURE OF GASTRI C POLYPS

A study of the diagnostic value of tissue eosinophil infiltration in the structure of polyps of the human gastrointestinal tract and surrounding tissues was carried out. We investigated intestinal biopsies from 189 patients aged 40–90 years with polyps, cancer, metastases. This retrospective study allows us to note the possibility of using eosinophils in the development of criteria for early malignancy and a promising outcome of neoplasms in the mucous membrane. Eosinophils are important players in intercellular interactions within the polyp structure and the tissues around it. The complete absence of eosinophils in the tissue of malignant polyps indicates the malignancy of the neoplasm. We revealed relationship between apoptosis and eosinophilic infiltration; both of them affect the outcome and prognosis of polyp development. Apoptosis induction by eosinophils and programmed cambium necrosis in tumor progression need to be further researched.

Comparative Genomics and Specific Functional Characteristics Analysis of Lactobacillus acidophilus

Lactobacillus acidophilus is a common kind of lactic acid bacteria usually found in the human gastrointestinal tract, oral cavity, vagina, and various fermented foods. At present, many studies have focused on the probiotic function and industrial application of L. acidophilus. Additionally, dozens of L. acidophilus strains have been genome sequenced, but there has been no research to compare them at the genomic level. In this study, 46 strains of L. acidophilus were performed comparative analyses to explore their genetic diversity. The results showed that all the L. acidophilus strains were divided into two clusters based on ANI values, phylogenetic analysis and whole genome comparison, due to the difference of their predicted gene composition of bacteriocin operon, CRISPR-Cas systems and prophages mainly. Additionally, L. acidophilus was a pan-genome open species with a difference in carbohydrates utilization, antibiotic resistance, EPS operon, surface layer protein operon and other functional gene composition. This work provides a better understanding of L. acidophilus from a genetic perspective, and offers a frame for the biotechnological potentiality of this species.

PBPK Modeling as a Tool for Predicting and Understanding Intestinal Metabolism of Uridine 5′-Diphospho-glucuronosyltransferase Substrates

Uridine 5′-diphospho-glucuronosyltransferases (UGTs) are expressed in the small intestines, but prediction of first-pass extraction from the related metabolism is not well studied. This work assesses physiologically based pharmacokinetic (PBPK) modeling as a tool for predicting intestinal metabolism due to UGTs in the human gastrointestinal tract. Available data for intestinal UGT expression levels and in vitro approaches that can be used to predict intestinal metabolism of UGT substrates are reviewed. Human PBPK models for UGT substrates with varying extents of UGT-mediated intestinal metabolism (lorazepam, oxazepam, naloxone, zidovudine, cabotegravir, raltegravir, and dolutegravir) have demonstrated utility for predicting the extent of intestinal metabolism. Drug–drug interactions (DDIs) of UGT1A1 substrates dolutegravir and raltegravir with UGT1A1 inhibitor atazanavir have been simulated, and the role of intestinal metabolism in these clinical DDIs examined. Utility of an in silico tool for predicting substrate specificity for UGTs is discussed. Improved in vitro tools to study metabolism for UGT compounds, such as coculture models for low clearance compounds and better understanding of optimal conditions for in vitro studies, may provide an opportunity for improved in vitro–in vivo extrapolation (IVIVE) and prospective predictions. PBPK modeling shows promise as a useful tool for predicting intestinal metabolism for UGT substrates.

Safety, efficacy, and maneuverability of a self-propelled capsule endoscope for observation of the human gastrointestinal tract

Background and study aims We developed a self-propelled capsule endoscope that can be controlled from outside the body with real-time observation. To improve the device, we conducted a clinical trial of total gastrointestinal capsule endoscopy in healthy subjects to ascertain whether our first-generation, self-propelled capsule endoscope was safe and effective for observing the entire human gastrointestinal tract. Patients and methods After adequate gastrointestinal pretreatment, five healthy subjects were instructed to swallow a self-propelling capsule endoscope and the safety of a complete gastrointestinal capsule endoscopy with this device was assessed. We also investigated basic problems associated with complete gastrointestinal capsule endoscopy. Results No adverse effects of the magnetic field were identified in any of the subjects. No mucosal damage was noted in any of the subjects with the use of our first-generation, self-propelling capsule endoscope. We found that it took longer than expected to observe the stomach; the view was compromised by the swallowed saliva. The pylorus was extremely difficult to navigate, and the endoscope’s fin sometimes got caught in the folds of the small intestine and colon. Conclusions To resolve the problems associated with the existing self-propelling capsule endoscope, it may be necessary to not only improve the capsule endoscopes, but also to control the environment within the gastrointestinal tract with medications and other means. Our results could guide other researchers in developing capsule endoscopes controllable from outside the body, thus allowing real-time observation.