An increase of multiple sclerosis (MS) incidence has been reported during the last decade, and this may be connected to environmental factors. This review article aims to encapsulate the current advances targeting the study of the gut–brain axis, which mediates the communication between the central nervous system and the gut microbiome. Clinical data arising from many research studies, which have assessed the effects of administered disease-modifying treatments in MS patients to the gut microbiome, are also recapitulated.

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Upon activation with pathogen-associated molecular patterns, metabolism of macrophages and dendritic cells is shifted from oxidative phosphorylation to aerobic glycolysis, which is considered important for proinflammatory cytokine production. Fragments of bacterial peptidoglycan (muramyl peptides) activate innate immune cells through nucleotide-binding oligomerization domain (NOD) 1 and/or NOD2 receptors. Here, we show that NOD1 and NOD2 agonists induce early glycolytic reprogramming of human monocyte-derived macrophages (MDM), which is similar to that induced by the Toll-like receptor 4 (TLR4) agonist lipopolysaccharide. This glycolytic reprogramming depends on Akt kinases, independent of mTOR complex 1 and is efficiently inhibited by 2-deoxy-d-glucose (2-DG) or by glucose starvation. 2-DG inhibits proinflammatory cytokine production by MDM and monocyte-derived dendritic cells activated by NOD1 or TLR4 agonists, except for tumor necrosis factor production by MDM, which is inhibited initially, but augmented 4 h after addition of agonists and later. However, 2-DG exerts these effects by inducing unfolded protein response rather than by inhibiting glycolysis. By contrast, glucose starvation does not cause unfolded protein response and, in normoxic conditions, only marginally affects proinflammatory cytokine production triggered through NOD1 or TLR4. In hypoxia mimicked by treating MDM with oligomycin (a mitochondrial ATP synthase inhibitor), both 2-DG and glucose starvation strongly suppress tumor necrosis factor and interleukin-6 production and compromise cell viability. In summary, the requirement of glycolytic reprogramming for proinflammatory cytokine production in normoxia is not obvious, and effects of 2-DG on cytokine responses should be interpreted cautiously. In hypoxia, however, glycolysis becomes critical for cytokine production and cell survival.

Bird migration is commonly defined as a seasonal movement between breeding and non-breeding grounds. It generally involves relatively straight and directed large-scale movements, with a latitudinal change, and specific daily activity patterns comprising less or no foraging and more traveling time. Our main objective was to describe how this general definition applies to seabirds. We investigated migration characteristics of 6 pelagic seabird species (little auk Alle alle, Atlantic puffin Fratercula arctica, common guillemot Uria aalge, Brünnich’s guillemot U. lomvia, black-legged kittiwake Rissa tridactyla and northern fulmars Fulmarus glacialis). We analysed an extensive geolocator positional and saltwater immersion dataset from 29 colonies in the North-East Atlantic and across several years (2008-2019). We used a novel method to identify active migration periods based on segmentation of time series of track characteristics (latitude, longitude, net-squared displacement). Additionally, we used the saltwater immersion data of geolocators to infer bird activity. We found that the 6 species had, on average, 3 to 4 migration periods and 2 to 3 distinct stationary areas during the non-breeding season. On average, seabirds spent the winter at lower latitudes than their breeding colonies and followed specific migration routes rather than non-directionally dispersing from their colonies. Differences in daily activity patterns were small between migratory and stationary periods, suggesting that all species continued to forage and rest while migrating, engaging in a ‘fly-and-forage’ migratory strategy. We thereby demonstrate the importance of habitats visited during seabird migrations as those that are not just flown over, but which may be important for re-fuelling.