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Commensal bacteria in gut lumen are known to interact with the enteric nervous system. Mao and colleagues test the effects of Lactobacillus rhamnosus and Bacteroides fragilis ex vivo, in the myenteric plexus, and find that the polysaccharide A is necessary for intestinal sensory neuron sensitization.

Glycoconjugate vaccines—such as those targeting some bacteria—couple a glycan to a protein to provide T cell help to B cells and induce polysaccharide-specific IgGs. T cell help has been thought to be conferred by recognition of the protein portion by T cells. Dennis Kasper and his colleagues now report that a glycan-peptide conjugate can induce T cells specific for the glycan moiety, which could help inform future glycoconjugate vaccine development.

Bacteroides fragilis is a member of the human intestinal microbiota. It is reported that a single molecule produced by this bacterium, polysaccharide A, can suppress the intestinal inflammatory response and thus protect from experimental colitis.

The authors identify AgcT as the glycosyltransferase required for synthesis of Bacteroides fragilis-derived α-galactosylceramides (BfaGCs), metabolites known to regulate natural killer T cells, and its structural homologue BgsB that synthesizes α-glycosyl diacylglycerols (aGDGs). They establish a functional link between the production of BfaGCs or aGDGs and the activity and development of natural killer T cells.

Interactions between programmed death ligand 2 (PD-L2) and its binding partner RGMb are downregulated by the gut microbiota, a mechanism that may be exploited to enhance the efficacy of PD-1-based cancer immunotherapies.

Polysaccharide A (PSA) from the human intestinal commensal Bacteroides fragilis mediates protection against the experimental autoimmune encephalomyelitis in mice. Here, Wang et al. show that the protective function of PSA is exerted through its action on CD39⁺regulatory CD4 T cells via Toll-like receptor 2 signalling.

APOL9a/b proteins coat mouse intestinal bacteria with high specificity, and genetic abolition of ceramide-1-phosphate synthesis pathways in the symbiote Bacteroides thetaiotaomicron significantly decreases this binding of APOL9a/b to the bacterium.

A diet–microorganism pathway involving conjugated linoleic acid, interleukin-18, intraepithelial lymphocytes and the transcription factor hepatocyte nuclear factor  4γ modulates the host mucosal immune system.

The symbiotic gut bacterium Bacteroides fragilis produces unique α-galactosylceramides from host dietary branched-chain amino acids, which are presented as CD1d ligands and immunomodulate natural killer T cells.

Metabolic labelling can be used to simultaneously tag peptidoglycan, lipopolysaccharide and capsular polysaccharide of live gut bacteria, and to label peptidoglycan in vivo, revealing host–bacteria interactions within the living mammalian host.

Neonatal mice are protected against infection with the enteric pathogen enterotoxigenic Escherichia coli by maternally derived natural antibodies as well as by maternal commensal microbiota that induce antibodies that recognize antigens expressed by  Enterobacteriaceae.

Both dietary and microbial factors influence the composition of the gut bile acid pool, which in turn modulates the frequencies and functionalities of RORγ-expressing colonic FOXP3⁺ regulatory T cells, contributing to protection from inflammatory colitis.

The commensal gut bacteriumBacteroides fragilismight be the key to a healthy immune system. A zwitterionic polysaccharide that is produced by this bacterium has immunomodulatory properties, and the authors suggest that this supports the 'hygiene hypothesis' at a molecular level.

NMDA receptors are complexes of NR1 and NR2 subunits that mediate excitatory synaptic transmission and have roles in neurological disorders. Here, a subunit-selective potentiator of NMDA receptors is identified, which may allow the evaluation of the functional roles of individual NMDA receptor subunits.

Triangulation of microbe–phenotype relationships is an effective method for reducing the noise inherent in microbiota studies and enabling identification of causal microbes of disease, which may be applicable to human microbiome studies.

A method for performing quantitative proteomics experiments in Caenorhabditis elegans using stable-isotope labeling of lysine is described. The method can be coupled with RNA interference to examine global effects on the proteome. Also in this issue, Larance et al. describe a very similar method.

A microfluidic intestine-on-a-chip that allows the control of physiologically relevant oxygen gradients, enables the extended coculture of living human intestinal epithelium with stable communities of aerobic and anaerobic human gut microbiota.

Cockburn et al. report that epidermal differentiation is a multi-day process through which cells undergo a continuum of transcriptional alterations initiated independently of cell cycle exit.

Fluorescently labeled commensal microbes can be tracked in vivo, allowing visualization of host–microbiota interactions in real time.

Roman Thomas and colleagues report exome sequencing of 29 small-cell lung cancers (SCLCs), 2 SCLC genomes and transcriptomes of 15 SCLCs. They identify recurrent mutations in the CREBBP, EP300 and MLL genes encoding histone modifiers. They identify mutations in SLIT2 and EPHA7, which have a role in axon guidance and cell migration, and focal amplifications of FGFR1.

Fatty acid transport from blood vessels to skeletal muscle, across endothelial cells, is regulated by the branched chain amino acid metabolite 3-hydroxy-isobutyrate. This finding provides a mechanistic explanation for the link between high levels of branched chain amino acids and diabetes.

Trabjerg et al. show that the activity of carnitine palmitoyl transferase 1 (CPT1) and lipid metabolism are associated with the disease progression of the SOD1 G93A mouse model mimicking a motor neuron disease Amyotrophic lateral sclerosis (ALS). This study suggests CPT1 as a potential therapeutic target in treating ALS.

Wild mice are genetically similar to laboratory mice, but have a distinct gut microbiota that protects from disease.

In mice treated with antibiotics to deplete commensal microbiota, there is a significant overhaul of host cellular disposition and function with CX3CR1+ mononuclear phagocytic cells carrying pathogenic and non-pathogenic administered bacteria to the (messenteric lymph node) MLN, resulting in T cell stimulation and IgA production.

Group BStreptococcus(GBS) is a pathogen of worldwide significance, and although prophylactic measures have reduced the number of infections, development of a vaccine remains an important goal. Here, the authors review the incidence of GBS and how new technologies are being applied in the search for a globally effective vaccine.