Modelling SARS-CoV-2 infection in a human alveolus microphysiological system.

The coronavirus 2019 pandemic has highlighted the importance of physiologically relevant models to assist preclinical research. Here, we describe the adaptation of a human alveolus microphysiological system (MPS) model consisting of primary human alveolar epithelial and lung microvascular endothelial cells to study infection with SARS-CoV-2 at Biosafety Level 3 facility. This infection model recapitulates breathing-like stretch and culture of epithelial cells at the air-liquid interface and resulted in clinically relevant cytopathic effects including cell rounding of alveolar type 2 cells and disruption of the tight junction protein occludin.

enhances HS production in .

Sulfate- and sulfite-reducing bacteria (SRB) are a group of strict anaerobes found within the human gut. , a sulfite-reducing bacterium which produces hydrogen sulfide (HS) from taurine and isethionate respiration, is a common member of the healthy commensal human gut microbiota but has been implicated in several disease states including inflammatory bowel disease and colorectal cancer. , one of the most prominent gut bacteria, has sulfatases which release sulfate, serving as a potential substrate for sulfate-reducing bacteria.

The human gut Bacteroides eggerthii expresses a new galactofuranose-containing lipooligosaccharide with weak immunostimulatory properties.

Lipopolysaccharides (LPS) decorating the cell surface of Gram-negative bacteria exhibit nuanced functionalities linked to their precise structural composition. However, despite their critical role in health and disease, information on the structure and function of LPS from members of the human gut microbiota is still limited. Here, we deciphered the complete structure of the LPS isolated from the human gut bacterium Bacteroides eggerthii 1_2_48FAA.

Multifrequency-STD NMR unveils the first Michaelis complex of an intramolecular trans-sialidase from Ruminococcus gnavus.

RgNanH is an intramolecular trans-sialidase expressed by the human gut symbiont Ruminococcus gnavus, to utilise intestinal sialylated mucin glycan epitopes. Its catalytic domain, belonging to glycoside hydrolase GH33 family, cleaves off terminal sialic acid residues from mucins, releasing 2,7-anhydro-Neu5Ac which is then used as metabolic substrate by R. gnavus to proliferate in the mucosal environment.

The human gut symbiont Ruminococcus gnavus displays strain-specific exopolysaccharides modulating the host immune response.

Ruminococcus gnavus is a prevalent member of the human gut microbiota and over-represented in inflammatory bowel diseases. R. gnavus ATCC 29149 was previously shown to produce a pro-inflammatory exopolysaccharide (EPS) referred to here as glucorhamnan-I or EPS.

Neurotransmitter recognition by human vesicular monoamine transporter 2.

Human vesicular monoamine transporter 2 (VMAT2), a member of the SLC18 family, plays a crucial role in regulating neurotransmitters in the brain by facilitating their uptake and storage within vesicles, preparing them for exocytotic release. Because of its central role in neurotransmitter signalling and neuroprotection, VMAT2 is a target for neurodegenerative diseases and movement disorders, with its inhibitor being used as therapeutics. Despite the importance of VMAT2 in pharmacophysiology, the molecular basis of VMAT2-mediated neurotransmitter transport and its inhibition remains unclear.

Human milk oligosaccharide 2'-fucosyllactose protects against high-fat diet-induced obesity by changing intestinal mucus production, composition and degradation linked to changes in gut microbiota and faecal proteome profiles in mice.

Objective: To decipher the mechanisms by which the major human milk oligosaccharide (HMO), 2'-fucosyllactose (2'FL), can affect body weight and fat mass gain on high-fat diet (HFD) feeding in mice. We wanted to elucidate whether 2'FL metabolic effects are linked with changes in intestinal mucus production and secretion, mucin glycosylation and degradation, as well as with the modulation of the gut microbiota, faecal proteome and endocannabinoid (eCB) system.

Results: 2'FL supplementation reduced HFD-induced obesity and glucose intolerance.

Characterisation of anhydro-sialic acid transporters from mucosa-associated bacteria.

Sialic acid (Sia) transporters are critical to the capacity of host-associated bacteria to utilise Sia for growth and/or cell surface modification. While N-acetyl-neuraminic acid (Neu5Ac)-specific transporters have been studied extensively, little is known on transporters dedicated to anhydro-Sia forms such as 2,7-anhydro-Neu5Ac (2,7-AN) or 2,3-dehydro-2-deoxy-Neu5Ac (Neu5Ac2en). Here, we used a Sia-transport-null strain of to investigate the function of members of anhydro-Sia transporter families previously identified by computational studies.

Role of mucin glycosylation in the gut microbiota-brain axis of core 3 O-glycan deficient mice.

Alterations in intestinal mucin glycosylation have been associated with increased intestinal permeability and sensitivity to inflammation and infection. Here, we used mice lacking core 3-derived O-glycans (C3GnT) to investigate the effect of impaired mucin glycosylation in the gut-brain axis. C3GnT mice showed altered microbial metabolites in the caecum associated with brain function such as dimethylglycine and N-acetyl-L-tyrosine profiles as compared to C3GnT littermates.

Microbe Profile: : the yin and yang of human gut symbionts.

is a human gut symbiont, part of the infant and adult gut microbiota and associated with intestinal and extra-intestinal disorders. mechanisms of adaptation to the gut are strain-specific and underpinned by the capacity of strains to utilize mucin and dietary glycans and produce bacteriocins and adhesins. Several potential mediators underpinning the association between strains and diseases have been identified, including the capacity to elicit a pro- or anti-inflammatory host response and modulate host metabolism, secondary bile acids and tryptophan metabolic pathways.

Ruminococcus gnavus: friend or foe for human health.

Ruminococcus gnavus was first identified in 1974 as a strict anaerobe in the gut of healthy individuals, and for several decades, its study has been limited to specific enzymes or bacteriocins. With the advent of metagenomics, R. gnavus has been associated both positively and negatively with an increasing number of intestinal and extraintestinal diseases from inflammatory bowel diseases to neurological disorders.

Sialidases and fucosidases of Akkermansia muciniphila are crucial for growth on mucin and nutrient sharing with mucus-associated gut bacteria.

The mucolytic human gut microbiota specialist Akkermansia muciniphila is proposed to boost mucin-secretion by the host, thereby being a key player in mucus turnover. Mucin glycan utilization requires the removal of protective caps, notably fucose and sialic acid, but the enzymatic details of this process remain largely unknown. Here, we describe the specificities of ten A.

Structure and function of microbial α-l-fucosidases: a mini review.

Fucose is a monosaccharide commonly found in mammalian, insect, microbial and plant glycans. The removal of terminal α-l-fucosyl residues from oligosaccharides and glycoconjugates is catalysed by α-l-fucosidases. To date, glycoside hydrolases (GHs) with exo-fucosidase activity on α-l-fucosylated substrates (EC 3.

Biochemical and structural basis of sialic acid utilization by gut microbes.

The human gastrointestinal (GI) tract harbors diverse microbial communities collectively known as the gut microbiota that exert a profound impact on human health and disease. The repartition and availability of sialic acid derivatives in the gut have a significant impact on the modulation of gut microbes and host susceptibility to infection and inflammation. Although N-acetylneuraminic acid (Neu5Ac) is the main form of sialic acids in humans, the sialic acid family regroups more than 50 structurally and chemically distinct modified derivatives.

Relationship between mucosa-associated gut microbiota and human diseases.

The mucus layer covering the gastrointestinal (GI) tract plays a critical role in maintaining gut homeostasis. In the colon, the inner mucus layer ensures commensal microbes are kept at a safe distance from the epithelium while mucin glycans in the outer mucus layer provide microbes with nutrients and binding sites. Microbes residing in the mucus form part of the so-called 'mucosa-associated microbiota' (MAM), a microbial community which, due to its close proximity to the epithelium, has a profound impact on immune and metabolic health by directly impacting gut barrier function and the immune system.

The role of the mucin-glycan foraging in the communication between the gut and the brain.

is a prevalent member of the human gut microbiota, which is over-represented in inflammatory bowel disease and neurological disorders. We previously showed that the ability of to forage on mucins is strain-dependent and associated with sialic acid metabolism. Here, we showed that mice monocolonized with ATCC 29149 (-mice) display changes in major sialic acid derivatives in their cecum content, blood, and brain, which is accompanied by a significant decrease in the percentage of sialylated residues in intestinal mucins relative to germ-free (GF) mice.

Biochemical Basis of Xylooligosaccharide Utilisation by Gut Bacteria.

Xylan is one of the major structural components of the plant cell wall. Xylan present in the human diet reaches the large intestine undigested and becomes a substrate to species of the gut microbiota. Here, we characterised the capacity of and strains to utilise xylan derivatives.

Development of a novel human intestinal model to elucidate the effect of anaerobic commensals on Escherichia coli infection.

The gut microbiota plays a crucial role in protecting against enteric infection. However, the underlying mechanisms are largely unknown owing to a lack of suitable experimental models. Although most gut commensals are anaerobic, intestinal epithelial cells require oxygen for survival.

Development of an exoglycosidase plate-based assay for detecting α1-3,4 fucosylation biomarker in individuals with HNF1A-MODY.

Maturity-onset diabetes of the young due to hepatocyte nuclear factor-1 alpha variants (HNF1A-MODY) causes monogenic diabetes. Individuals carrying damaging variants in HNF1A show decreased levels of α1-3,4 fucosylation, as demonstrated on antennary fucosylation of blood plasma N-glycans. The excellent diagnostic performance of this glycan biomarker in blood plasma N-glycans of individuals with HNF1A-MODY has been demonstrated using liquid chromatography methods.

Lipopolysaccharide associated with β-2,6 fructan mediates TLR4-dependent immunomodulatory activity in vitro.

Levan, a β-2,6 fructofuranose polymer produced by microbial species, has been reported for its immunomodulatory properties via interaction with toll-like receptor 4 (TLR4) which recognises lipopolysaccharide (LPS). However, the molecular mechanisms underlying these interactions remain elusive. Here, we investigated the immunomodulatory properties of levan using thoroughly-purified and characterised samples from Erwinia herbicola and other sources.

The Effects of Human Milk Oligosaccharides on Gut Microbiota, Metabolite Profiles and Host Mucosal Response in Patients with Irritable Bowel Syndrome.

Background: Human milk oligosaccharide supplementation safely modulates fecal bifidobacteria abundance and holds the potential to manage symptoms in irritable bowel syndrome (IBS). Here, we aimed to determine the role of a 4:1 mix of 2'-O-fucosyllactose and lacto-N-neotetraose (2'FL/LNnT) on the modulation of the gut microbiota composition and host mucosal response, as well as the link between the bifidobacteria abundance and metabolite modulation, in IBS patients.

Methods: Biological samples were collected from IBS patients ( = 58) at baseline and week 4 post-supplementation with placebo, 5 g or 10 g doses of 2'FL/LNnT.