Necrotizing Enterocolitis: The Role of Hypoxia, Gut Microbiome, and Microbial Metabolites.

Necrotizing enterocolitis (NEC) is a life-threatening disease that predominantly affects very low birth weight preterm infants. Development of NEC in preterm infants is accompanied by high mortality. Surgical treatment of NEC can be complicated by short bowel syndrome, intestinal failure, parenteral nutrition-associated liver disease, and neurodevelopmental delay. Issues surrounding pathogenesis, prevention, and treatment of NEC remain unclear. This review summarizes data on prenatal risk factors for NEC, the role of pre-eclampsia, and intrauterine growth retardation in the pathogenesis of NEC. The role of hypoxia in NEC is discussed. Recent data on the role of the intestinal microbiome in the development of NEC, and features of the metabolome that can serve as potential biomarkers, are presented. The Pseudomonadota phylum is known to be associated with NEC in preterm neonates, and the role of other bacteria and their metabolites in NEC pathogenesis is also discussed. The most promising approaches for preventing and treating NEC are summarized.

Bad "Good" Bile Acids and Gut Microbiota Dysbiosis in Inflammatory Bowel Disease: Mice and Humans Are Not the Same.

The effects of deoxycholic acid (DCA) on the intestinal microbiota, bile acid (BA) metabolism, and intestinal epithelium can be influenced by various factors. Depending on the specific conditions, DCA can be "bad" (proinflammatory) or "good" (anti-inflammatory). Mouse models of colitis show an increase in conjugated BAs and gut dysbiosis, including DCA-related dysbiosis, with a significant decrease in bile salt hydrolase (bsh) gene-containing taxa. Human patients with inflammatory bowel disease demonstrate, primarily, a decrease in bile acid-inducible (bai) gene-containing taxa and a deficiency in secondary BAs, suggesting their anti-inflammatory role.

Acceptive Immunity: The Role of Fucosylated Glycans in Human Host-Microbiome Interactions.

The growth in the number of chronic non-communicable diseases in the second half of the past century and in the first two decades of the new century is largely due to the disruption of the relationship between the human body and its symbiotic microbiota, and not pathogens. The interaction of the human immune system with symbionts is not accompanied by inflammation, but is a physiological norm. This is achieved via microbiota control by the immune system through a complex balance of pro-inflammatory and suppressive responses, and only a disturbance of this balance can trigger pathophysiological mechanisms. This review discusses the establishment of homeostatic relationships during immune system development and intestinal bacterial colonization through the interaction of milk glycans, mucins, and secretory immunoglobulins. In particular, the role of fucose and fucosylated glycans in the mechanism of interactions between host epithelial and immune cells is discussed.

He who controls Clostridia and Bacteroidia controls the gut microbiome: The concept of targeted probiotics to restore the balance of keystone taxa in irritable bowel syndrome.

This article describes the concept of probiotics for patients with irritable bowel syndrome to target functionally active bacteria predominantly belonging to the Clostridia and Bacteroidia, which play a key role in maintaining the balance of the gut microbiota.

Gastrointestinal microbiome and Helicobacter pylori: Eradicate, leave it as it is, or take a personalized benefit-risk approach?

Helicobacter pylori (H. pylori) is generally regarded as a human pathogen and a class 1 carcinogen, etiologically related to gastric and duodenal ulcers, gastric cancer, and mucosa-associated lymphoid tissue lymphoma. However, H. pylori can also be regarded as a commensal symbiont. Unlike other pathogenic/ opportunistic bacteria, H. pylori colonization in infancy is facilitated by T helper type 2 immunity and leads to the development of immune tolerance. Fucosylated gastric mucin glycans, which are an important part of the innate and adaptive immune system, mediate the adhesion of H. pylori to the surface of the gastric epithelium, contributing to successful colonization. H. pylori may have beneficial effects on the host by regulating gastrointestinal (GI) microbiota and protecting against some allergic and autoimmune disorders and inflammatory bowel disease. The potential protective role against inflammatory bowel disease may be related to both modulation of the gut microbiota and the immunomodulatory properties of H. pylori. The inverse association between H. pylori and some potentially proinflammatory and/or procarcinogenic bacteria may suggest it regulates the GI microbiota. Eradication of H. pylori can cause various adverse effects and alter the GI microbiota, leading to short-term or long-term dysbiosis. Overall, studies have shown that gastric Actinobacteria decrease after H. pylori eradication, Proteobacteria increase during short-term follow-up and then return to baseline levels, and Enterobacteriaceae and Enterococcus increase in the short-term and interim follow-up. Various gastric mucosal bacteria (Actinomyces, Granulicatella, Parvimonas, Peptostreptococcus, Prevotella, Rothia, Streptococcus, Rhodococcus, and Lactobacillus) may contribute to precancerous gastric lesions and cancer itself after H. pylori eradication. H. pylori eradication can also lead to dysbiosis of the gut microbiota, with increased Proteobacteria and decreased Bacteroidetes and Actinobacteria. The increase in gut Proteobacteria may contribute to adverse effects during and after eradication. The decrease in Actinobacteria, which are pivotal in the maintenance of gut homeostasis, can persist for > 6 mo after H. pylori eradication. Furthermore, H. pylori eradication can alter the metabolism of gastric and intestinal bacteria. Given the available data, eradication cannot be an unconditional recommendation in every case of H. pylori infection, and the decision to eradicate H. pylori should be based on an assessment of the benefit-risk ratio for the individual patient. Thus, the current guidelines based on the unconditional "test-and-treat" strategy should be revised. The most cautious and careful approach should be taken in elderly patients with multiple eradication failures since repeated eradication can cause antibiotic-associated diarrhea, including severe Clostridioides difficile-associated diarrhea and colitis and antibiotic-associated hemorrhagic colitis due to Klebsiella oxytoca. Furthermore, since eradication therapy with antibiotics and proton pump inhibitors can lead to serious adverse effects and/or dysbiosis of the GI microbiota, supplementation of probiotics, prebiotics, and microbial metabolites (e.g., butyrate + inulin) should be considered to decrease the negative effects of eradication.

CE with Cu2+ ions and 2-hydroxypropyl-ß-cyclodextrin additives for the investigation of amino acids composition of the culture medium in a cellular model of non-alcoholic fatty liver disease.

CE method with CuSO4 and 2-hydroxypropyl-ß-cyclodextrin additives in sodium acetate background electrolyte pH 4.3 for the simultaneous determination of amino acids and lactic acid was adapted for the comparative study of metabolism in "healthy" and non-alcoholic fatty liver disease model cells HepG2. In vitro model of the disease was developed by exposure HepG2 cells with oleate and palmitate to simulate an excessive flow of fatty acids into hepatocytes. The model was proven to be consistent with the disease pathophysiology, since intracellular triglyceride and cytokine interleukin 8 levels were increased, while cells viability was decreased. In order to check whether the metabolism of amino acids changes in pathology, we proposed sample preparation of culture medium and characterized the CE method by evaluating linear dynamic range, repeatability and intermediate precision of peak areas and migration times, accuracy (recovery rate and trueness estimated by reference method), detection limits and quantitation limits. The method proved to be sensitive, reliable and highly accurate for the quantitation of amino acids and lactic acid. The concentrations of amino acids in the culture medium of healthy and the disease model cells were measured and altered levels of Arg, Ala, Glu, Gln and lactic acid have been found in comparison to health control.

Intestinal microbiome changes in an infant with right atrial isomerism and recurrent necrotizing enterocolitis: A case report and review of literature.

BACKGROUND: Necrotizing enterocolitis (NEC) is a multifactorial disease that predominantly affects premature neonates. Intestinal dysbiosis plays a critical role in NEC pathogenesis in premature neonates. The main risk factor for NEC in term infants is mesenteric hypoperfusion associated with ductal-dependent congenital heart disease (CHD) that eventually leads to intestinal ischemia. The incidence of NEC in neonates with critical CHD is 6.8%-13%. However, the role of the intestinal microbiome in NEC pathogenesis in infants with ductal-dependent CHD remains unclear. CASE SUMMARY: A male term neonate with right atrial isomerism underwent modified Blalock-Taussig shunt placement on the 14th day of life and had persistent mesenteric hypoperfusion after surgery. The patient had episodes of NEC stage IIA on the 1st and 28th days after cardiac surgery. Fecal microbial composition was analyzed before and after cardiac surgery by sequencing region V4 of the 16S rRNA gene. Before surgery, species belonging to genera Veillonella and Clostridia and class Gammaproteobacteria were detected, Bifidobacteriaceae showed a low abundance. The first NEC episode was associated with postoperative hemodynamic instability, intestinal ischemia-reperfusion injury during cardiopulmonary bypass, and a high abundance of Clostridium paraputrificum (Clostridium sensu stricto I) (56.1%). Antibacterial therapy after the first NEC episode resulted in increased abundance of Gammaproteobacteria, decreased abundance of Firmicutes, and low alpha diversity. These changes in the microbial composition promoted the growth of Clostridium sensu stricto I (72.0%) before the second NEC episode. CONCLUSION: A high abundance of Clostridium sensu stricto I and mesenteric hypoperfusion may have contributed to NEC in the present case.

Whole-Genome Sequencing of Lactobacillus helveticus D75 and D76 Confirms Safety and Probiotic Potential.

Whole-genome DNA sequencing of Lactobacillus D75 and D76 strains (Vitaflor, Russia) was determined using the PacBio RS II platform, which was followed by de novo assembly with SMRT Portal 2.3.0. The average nucleotide identity (ANI) test showed that both strains belong to the Lactobacillus helveticus, but not to the L. acidophilus, as previously assumed. In addition, 31 exopolysaccharide (EPS) production genes (nine of which form a single genetic cluster), 13 adhesion genes, 38 milk protein and 11 milk sugar utilization genes, 13 genes for and against specific antagonistic activity, eight antibiotic resistance genes, and also three CRISPR blocks and eight Cas I-B system genes were identified in the genomes of both strains. The expression of bacteriocin helveticin J genes was confirmed. In fact, the presence of identified genes suggests that L. helveticus D75 and D76 are able to form biofilms on the outer mucin layer, inhibit the growth of pathogens and pathobionts, utilize milk substrates with the formation of digestible milk sugars and bioactive peptides, resist bacteriophages, show some genome-determined resistance to antibiotics, and stimulate the host's immune system. Pathogenicity genes have not been identified. The study results confirm the safety and high probiotic potential of the strains.

Metabolomic Biomarkers in Gynecology: A Treasure Path or a False Path?

Omic-technologies (genomics, transcriptomics, proteomics and metabolomics) have become more important in current medical science. Among them, it is metabolomics that most accurately reflects the minor changes in body functioning, as it focuses on metabolome - the group of the metabolism products, both intermediate and end. Therefore, metabolomics is actively engaged in fundamental and clinical studies and search for potential biomarkers. The biomarker could be used in diagnostics, management and stratification of the patients, as well as in prognosing the outcomes. The good example is gynecology, since many gynecological diseases lack effective biomarkers. In the current review, we aimed to summarize the results of the studies, devoted to the search of potential metabolomic biomarkers for the most common gynecological diseases.

Targeted Probiotics Against Bacterial-Fungal Biofilms: A New Concept Seems to Bring Us Closer to Microbiome-modulating Therapy for Inflammatory Bowel Disease.

This article describes the concept of microbiome-modulating therapy for inflammatory bowel diseases using targeted probiotics. A designed probiotic composition is discussed as an example, the targets for which are polymicrobial bacterial-fungal biofilms specific for Crohn's disease.

Helicobacter pylori and Inflammatory Bowel Disease: An Unresolved Enigma.

The article describes the hypothesis that there may be a noncausal relationship between Helicobacter pylori infection and inflammatory bowel disease (IBD) that is related to the host mucin glycan fucosylation status in the gastrointestinal tract. The proposed hypothesis may explain why IBD is less prevalent in patients with H. pylori, and no increased risk of IBD is seen after H. pylori eradication therapy, as was shown in the study by Tanner et al.