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ObjectiveAntimicrobial C-type lectin regenerating islet-derived 3 gamma (REG3G) is suppressed in the small intestine during chronic ethanol feeding. Our aim was to determine the mechanism that underlies REG3G suppression during experimental alcoholic liver disease.DesignInterleukin 22 (IL-22) regulates expression of REG3G. Therefore, we investigated the role of IL-22 in mice subjected to chronic-binge ethanol feeding (NIAAA model).ResultsIn a mouse model of alcoholic liver disease, we found that type 3 innate lymphoid cells produce lower levels of IL-22. Reduced IL-22 production was the result of ethanol-induced dysbiosis and lower intestinal levels of indole-3-acetic acid (IAA), a microbiota-derived ligand of the aryl hydrocarbon receptor (AHR), which regulates expression of IL-22. Importantly, faecal levels of IAA were also found to be lower in patients with alcoholic hepatitis compared with healthy controls. Supplementation to restore intestinal levels of IAA protected mice from ethanol-induced steatohepatitis by inducing intestinal expression of IL-22 and REG3G, which prevented translocation of bacteria to liver. We engineered Lactobacillus reuteri to produce IL-22 (L. reuteri/IL-22) and fed them to mice along with the ethanol diet; these mice had reduced liver damage, inflammation and bacterial translocation to the liver compared with mice fed an isogenic control strain and upregulated expression of REG3G in intestine. However, L. reuteri/IL-22 did not reduce ethanol-induced liver disease in Reg3g-/- mice.ConclusionEthanol-associated dysbiosis reduces levels of IAA and activation of the AHR to decrease expression of IL-22 in the intestine, leading to reduced expression of REG3G; this results in bacterial translocation to the liver and steatohepatitis. Bacteria engineered to produce IL-22 induce expression of REG3G to reduce ethanol-induced steatohepatitis.

Comprehension of underlying mechanisms of probiotic action will support rationale selection of probiotic strains and targeted clinical study design with a higher likelihood of success. This will consequently contribute to better substantiation of health claims. Here, we aim to provide a perspective from a microbiology point of view that such comprehensive understanding is not straightforward. We show examples of well-documented probiotic effector molecules in Lactobacillus and Bifidobacterium strains, including surface-located molecules such as specific pili, S-layer proteins, exopolysaccharides, muropeptides, as well as more widely produced metabolites such as tryptophan-related and histamine-related metabolites, CpG-rich DNA, and various enzymes such as lactase and bile salt hydrolases. We also present recent advances in genetic tool development, microbiome analyses and model systems, as well as perspectives on how the field could further progress. This opinion is based on a discussion group organized at the annual meeting of the International Scientific Association on Probiotics and Prebiotics (ISAPP) in June 2017.

Gluco‐oligosaccharides (GlcOS) are potential prebiotics that positively modulate beneficial gut commensals like lactobacilli. For the rational design of GlcOS as prebiotics or combined with lactobacilli as synbiotics, it is important to establish the structure requirements of GlcOS and specificity toward lactobacilli. Herein, the utilization of 10 GlcOS with varied degrees of polymerization (DP) and glycosidic linkages by 7 lactobacilli strains (Levilactobacillus brevis ATCC 8287, Limosilactobacillus reuteri ATCC PTA 6475, Lacticaseibacillus rhamnosus ATCC 53103, Lentilactobacillus buchneri ATCC 4005, Limosilactobacillus fermentum FUA 3589, Lactiplantibacillus plantarum WCFS1, and Lactobacillus gasseri ATCC 33323) was studied. L. brevis ATCC 8287 was the only strain that grew on α/β‐(1→4/6) linked disaccharides, whereas other strains showed diverse patterns, dependent on the availability of genes encoding sugar transporters and catabolic enzymes. The effect of DP on GlcOS utilization was strain dependent. β‐(1→4) Linked cello‐oligosaccharides (COS) supported the growth of L. brevis ATCC 8287 and L. plantarum WCFS1, and shorter COS (DP 2–3) were preferentially utilized over longer COS (DP 4–7) (consumption ≥90% vs. 40%–60%). α‐(1→4) Linked maltotriose and maltodextrin (DP 2–11) were effectively utilized by L. brevis ATCC 8287, L. reuteri ATCC 6475, and L. plantarum WCFS1, but not L. fermentum FUA 3589. Growth of L. brevis ATCC 8287 on branched isomalto‐oligosaccharides (DP 2–6) suggested preferential consumption of DP 2–3, but no preference between α‐(1→6) and α‐(1→4) linkages. The knowledge of the structure‐specific GlcOS utilization by different lactobacilli from this study helps the structural rationale of GlcOS for prebiotic development. [ABSTRACT FROM AUTHOR]

The genome of Lactobacillus salivarius UCC118 includes a 242-kb megaplasmid, pMP118. We now show that 33 strains of L. salivarius isolated from humans and animals all harbor a megaplasmid, which hybridized with the repA and repE replication origin probes of pMP118. Linear megaplasmids that did not hybridize with the pMP118 repA probe were also found in some strains of L. salivarius, showing for the first time that a lactic acid bacterium has multiple megaplasmids. Phylogenetic analysis of the repE and groEL sequences of 28 L. salivarius strains suggested similar evolutionary paths for the chromosome and megaplasmid. Although the replication origin of circular megaplasmids in L. salivarius was highly conserved, genotypic and phenotypic comparisons revealed significant variation between megaplasmid-encoded traits. Furthermore, megaplasmids of sizes ranging from 120 kb to 490 kb were present in seven strains belonging to six other Lactobacillus species from among 91 strains and 47 species tested. The discovery of the widespread presence of megaplasmids in L. salivarius, and restricted carriage by other Lactobacillus species, provides an opportunity to study the contribution of large extrachromosomal replicons to the biology of Lactobacillus.