Effect of maternal HIV status on the early neonatal microbiome.

Microbiome disruption is a proposed mechanism for the observed differences in child health outcomes by maternal HIV status, but the early neonatal microbiome of HIV-exposed (HE) newborns is not well studied. We used 16S ribosomal ribonucleic acid sequencing to analyze the microbiome composition of nasal, skin, and rectal samples collected ≤72 hours after birth from 57 hospitalized neonates in Botswana, 33% of whom were HE. Beta diversity differed by anatomic compartment (p=.

Increased reflux secondary bile acids are associated with changes to the microbiome and transcriptome in Barrett's esophagus.

Bile acids are a major component of gastro-esophageal refluxate, thought to contribute to the development of Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC). As the microbiome shifts with EAC progression and bile acids influence bacterial composition, we examined these connections in a multi-center, cross-sectional study. We analyzed biospecimens from patients undergoing endoscopy using LC-MS to quantify bile acids in gastric aspirates, 16S rRNA sequencing for tissue microbiome profiling, and RNA sequencing on BE or cardia tissue.

Enhancing outcomes in medically inoperable early-stage NSCLC with gut-targeted antibiotics and stereotactic body radiotherapy: results from a randomized pilot study.

Background: Gut microbiota modulation is an emerging strategy to improve cancer therapy outcomes. This study evaluated the safety and therapeutic potential of combining oral vancomycin-a non-absorbed, gut-restricted antibiotic with primary activity against gram-positive bacteria-with stereotactic body radiotherapy (SBRT) in early-stage non-small cell lung cancer (NSCLC). The underlying hypothesis was that vancomycin-induced changes in gut microbiota could enhance the antitumor effects of SBRT.

Dietary Fiber Modulates the Window of Susceptibility to Clostridioides difficile Infection.

Background & Aims: Clostridioides difficile epidemiology is rapidly evolving, and understanding the factors that contribute to one's risk of C difficile infection (CDI) is urgently needed. Based on our observations in a dietary intervention study, we hypothesized that fiber modulates susceptibility to C difficile after antibiotic exposure and investigated this using human specimens and murine models.

Methods: To determine whether fiber impacts factors known to mediate colonization resistance against C difficile, we investigated bile acid and microbiota composition in human subjects consuming a low-fiber diet.

Gut metagenomes reveal interactions between dietary restriction, ageing and the microbiome in genetically diverse mice.

The gut microbiome changes with age and has been proposed to mediate the benefit of lifespan-extending interventions such as dietary restriction. However, the causes and consequences of microbiome ageing and the potential of such interventions remain unclear. Here we analysed 2,997 metagenomes collected longitudinally from 913 deeply phenotyped, genetically diverse mice to investigate interactions between the microbiome, ageing, dietary restriction (caloric restriction and fasting), host genetics and a range of health parameters.

A pro-inflammatory diet is associated with growth and virulence of Escherichia coli in pediatric Crohn's disease.

Background And Aims: Epidemiological studies have suggested an association between the inflammatory potential of dietary patterns and Crohn's disease (CD). However, the relationships of these inflammatory dietary determinants with the microbiome remain largely unknown. In this cross-sectional study, we evaluate the association between the inflammatory potential of habitual diet, as assessed by the modified Children-Dietary Inflammatory Index (mC-DII), and the fecal microbiome and metabolome of children with CD in comparison to healthy children.

Antibiotic exposure is associated with minimal gut microbiome perturbations in healthy term infants.

Background: The evolving infant gut microbiome influences host immune development and later health outcomes. Early antibiotic exposure could impact microbiome development and contribute to poor outcomes. Here, we use a prospective longitudinal birth cohort of n = 323 healthy term African American children to determine the association between antibiotic exposure and the gut microbiome through shotgun metagenomics sequencing as well as bile acid profiles through liquid chromatography-mass spectrometry.

Concomitant suppression of COX-1 and COX-2 is insufficient to induce enteropathy associated with chronic NSAID use.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most widely used medications for the management of chronic pain; however, they are associated with numerous gastrointestinal (GI) adverse events. Although many mechanisms have been suggested, NSAID-induced enteropathy has been thought to be primarily due to inhibition of both cyclooxygenases (COX) -1 and -2, which results in suppression of prostaglandin synthesis. Yet surprisingly, we found that concomitant postnatal deletion of and over 10 months failed to cause intestinal injury in mice unless they were treated with naproxen or its structural analog, phenylpropionic acid, which is not a COX inhibitor.

Metal availability shapes early life microbial ecology and community succession.

The gut microbiota plays a critical role in human health and disease. Microbial community assembly and succession early in life are influenced by numerous factors. In turn, assembly of this microbial community is known to influence the host, including immune system development, and has been linked to outcomes later in life.

A quantitative approach to measure and predict microbiome response to antibiotics.

Unlabelled: Although antibiotics induce sizable perturbations in the human microbiome, we lack a systematic and quantitative method to measure and predict the microbiome's response to specific antibiotics. Here, we introduce such a method, which takes the form of a microbiome response index (MiRIx) for each antibiotic. Antibiotic-specific MiRIx values quantify the overall susceptibility of the microbiota to an antibiotic, based on databases of bacterial phenotypes and published data on intrinsic antibiotic susceptibility.

Unassigning bacterial species for microbiome studies.

The method of 16S rRNA marker gene sequencing has fueled microbiome research and continues to be relevant. A perceived weakness of the method is that taxonomic assignments are not possible to make at the rank of species. We show that by working to bacterial or archaeal species membership, we can provide an answer that is more accurate and useful.

Distinct intestinal microbial signatures linked to accelerated systemic and intestinal biological aging.

Background: People living with HIV (PLWH), even when viral replication is controlled through antiretroviral therapy (ART), experience persistent inflammation. This inflammation is partly attributed to intestinal microbial dysbiosis and translocation, which may lead to non-AIDS-related aging-associated comorbidities. The extent to which living with HIV - influenced by the infection itself, ART usage, sexual orientation, or other associated factors - affects the biological age of the intestines is unclear.

Bile salt hydrolase catalyses formation of amine-conjugated bile acids.

Bacteria in the gastrointestinal tract produce amino acid bile acid amidates that can affect host-mediated metabolic processes; however, the bacterial gene(s) responsible for their production remain unknown. Herein, we report that bile salt hydrolase (BSH) possesses dual functions in bile acid metabolism. Specifically, we identified a previously unknown role for BSH as an amine N-acyltransferase that conjugates amines to bile acids, thus forming bacterial bile acid amidates (BBAAs).

Distinct Intestinal Microbial Signatures Linked to Accelerated Biological Aging in People with HIV.

Background: People with HIV (PWH), even with controlled viral replication through antiretroviral therapy (ART), experience persistent inflammation. This is partly due to intestinal microbial dysbiosis and translocation. Such ongoing inflammation may lead to the development of non-AIDS-related aging-associated comorbidities.

Enterobacteriaceae Growth Promotion by Intestinal Acylcarnitines, a Biomarker of Dysbiosis in Inflammatory Bowel Disease.

Background & Aims: Altered plasma acylcarnitine levels are well-known biomarkers for a variety of mitochondrial fatty acid oxidation disorders and can be used as an alternative energy source for the intestinal epithelium when short-chain fatty acids are low. These membrane-permeable fatty acid intermediates are excreted into the gut lumen via bile and are increased in the feces of patients with inflammatory bowel disease (IBD).

Methods: Herein, based on studies in human subjects, animal models, and bacterial cultures, we show a strong positive correlation between fecal carnitine and acylcarnitines and the abundance of Enterobacteriaceae in IBD where they can be consumed by bacteria both in vitro and in vivo.

Strain GG (LGG) Regulate Gut Microbial Metabolites, an In Vitro Study Using Three Mature Human Gut Microbial Cultures in a Simulator of Human Intestinal Microbial Ecosystem (SHIME).

In the present research, we investigated changes in the gut metabolome that occurred in response to the administration of the strain GG (LGG). The probiotics were added to the ascending colon region of mature microbial communities established in a human intestinal microbial ecosystem simulator. Shotgun metagenomic sequencing and metabolome analysis suggested that the changes in microbial community composition corresponded with changes to metabolic output, and we can infer linkages between some metabolites and microorganisms.

IgA deficiency destabilizes homeostasis toward intestinal microbes and increases systemic immune dysregulation.

The ability of most patients with selective immunoglobulin A (IgA) deficiency (SIgAD) to remain apparently healthy has been a persistent clinical conundrum. Compensatory mechanisms, including IgM, have been proposed, yet it remains unclear how secretory IgA and IgM work together in the mucosal system and, on a larger scale, whether the systemic and mucosal anti-commensal responses are redundant or have unique features. To address this gap in knowledge, we developed an integrated host-commensal approach combining microbial flow cytometry and metagenomic sequencing (mFLOW-Seq) to comprehensively define which microbes induce mucosal and systemic antibodies.

SARS-CoV-2-specific T cells in unexposed adults display broad trafficking potential and cross-react with commensal antigens.

The baseline composition of T cells directly affects later response to pathogens, but the complexity of precursor states remains poorly defined. Here, we examined the baseline state of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific T cells in unexposed individuals. SARS-CoV-2-specific CD4 T cells were identified in prepandemic blood samples by major histocompatibility complex (MHC) class II tetramer staining and enrichment.

Dietary fiber-based regulation of bile salt hydrolase activity in the gut microbiota and its relevance to human disease.

Complications of short bowel syndrome (SBS) include malabsorption and bacterial overgrowth, requiring prolonged dependence on parenteral nutrition (PN). We hypothesized that the intolerance of whole food in some SBS patients might be due to the effect of dietary fiber on the gut microbiome. Shotgun metagenomic sequencing and targeted metabolomics were performed using biospecimens collected from 55 children with SBS and a murine dietary fiber model.