Propionic Acid Driven by the Lactobacillus johnsonii Culture Supernatant Alleviates Colitis by Inhibiting M1 Macrophage Polarization by Modulating the MAPK Pathway in Mice.

In this study, we investigated the effects of Lactobacillus johnsonii on the mouse colitis model. The results showed that the supernatant of the L. johnsonii culture alleviated colitis and remodeled gut microbiota, represented by an increased abundance of bacteria producing short-chain fatty acids, leading to an increased concentration of propionic acid in the intestine. Further studies revealed that propionic acid inhibited activation of the MAPK signaling pathway and polarization of M1 macrophages. Macrophage clearance assays confirmed that macrophages are indispensable for alleviating colitis through propionic acid. In vitro experiments showed that propionic acid directly inhibited the MAPK signaling pathway in macrophages and reduced M1 macrophage polarization, thereby inhibiting the secretion of pro-inflammatory cytokines. These findings improve our understanding of how L. johnsonii attenuates inflammatory bowel disease (IBD) and provide valuable insights for identifying molecular targets for IBD treatment in the future.

Limosilactobacillus mucosae-derived extracellular vesicles modulates macrophage phenotype and orchestrates gut homeostasis in a diarrheal piglet model.

The diarrheal disease causes high mortality, especially in children and young animals. The gut microbiome is strongly associated with diarrheal disease, and some specific strains of bacteria have demonstrated antidiarrheal effects. However, the antidiarrheal mechanisms of probiotic strains have not been elucidated. Here, we used neonatal piglets as a translational model and found that gut microbiota dysbiosis observed in diarrheal piglets was mainly characterized by a deficiency of Lactobacillus, an abundance of Escherichia coli, and enriched lipopolysaccharide biosynthesis. Limosilactobacillus mucosae and Limosilactobacillus reuteri were a signature bacterium that differentiated healthy and diarrheal piglets. Germ-free (GF) mice transplanted with fecal microbiota from diarrheal piglets reproduced diarrheal disease symptoms. Administration of Limosilactobacillus mucosae but not Limosilactobacillus reuteri alleviated diarrheal disease symptoms induced by fecal microbiota of diarrheal piglets and by ETEC K88 challenge. Notably, Limosilactobacillus mucosae-derived extracellular vesicles alleviated diarrheal disease symptoms caused by ETEC K88 by regulating macrophage phenotypes. Macrophage elimination experiments demonstrated that the extracellular vesicles alleviated diarrheal disease symptoms in a macrophage-dependent manner. Our findings provide insights into the pathogenesis of diarrheal disease from the perspective of intestinal microbiota and the development of probiotic-based antidiarrheal therapeutic strategies.

Landscapes of Enteric Virome Signatures in Early-Weaned Piglets.

Diarrhea caused by early-weaning-induced stress can increase mortality rates and reduce growth performance of piglets, seriously harming the livestock industry. To date, studies on the gut microbiome of early-weaned piglets have focused almost exclusively on bacteria, while studies on their gut virome are extremely lacking. Here, we used metagenomic and metatranscriptomic sequencing combined with bioinformatic analysis techniques to preliminarily characterize the intestinal virome of early-weaned piglets at different biological classification levels. The alpha diversity of enteroviruses was generally elevated in early-weaned piglets with diarrhea, compared to healthy piglets, whereas the two groups of piglets showed no significant difference in beta diversity. In addition, the species compositions of the gut virome were similar between healthy piglets and piglets with diarrhea, while their respective dominant species were somewhat different. We also identified 58 differential DNA viruses and 16 differential RNA viruses between the two groups of piglets at all biological taxonomic levels. Of these, 1 (family Dhakavirus) and 6 (phylum Artverviricota, class Revtraviricetes, order Ortervirales, family Retroviridae, genus Gammaretrovirus, and species Kirsten murine sarcoma virus) specific viruses disappeared from the intestines of healthy piglets and piglets with diarrhea, respectively. Moreover, we found that some DNA and RNA viruses formed strong correlations among themselves or between them. IMPORTANCE This study systematically reveals the biological diversity, structure, and composition of intestinal DNA and RNA virus profiles in early-weaned piglets. Furthermore, characteristics of differences in gut viromes between early-weaned healthy piglets and piglets with diarrhea were also elucidated. Importantly, some potential biomarkers for early-weaned piglets with diarrhea were identified. These findings fill a gap for the early-weaned piglet gut virome and lay the foundation for the development of strategies to target enteroviruses for the prevention and treatment of early-weaning-induced piglet diarrhea.

Human Fecal Microbiota Transplantation Reduces the Susceptibility to Dextran Sulfate Sodium-Induced Germ-Free Mouse Colitis.

In clinical practice, fecal microbiota transplantation (FMT) has been used to treat inflammatory bowel disease (IBD), and has shown certain effects. However, the selection of FMT donors and the mechanism underlying the effect of FMT intervention in IBD require further exploration. In this study, dextran sodium sulfate (DSS)-induced colitis mice were used to determine the differences in the protection of colitis symptoms, inflammation, and intestinal barrier, by FMT from two donors. Intriguingly, pre-administration of healthy bacterial fluid significantly relieved the symptoms of colitis compared to the ulcerative colitis (UC) bacteria. In addition, healthy donor (HD) bacteria significantly reduced the levels of inflammatory markers Myeloperoxidase (MPO) and Eosinophil peroxidase (EPO), and various pro-inflammatory factors, in colitis mice, and increased the secretion of the anti-inflammatory factor IL-10. Metagenomic sequencing indicated higher species diversity and higher abundance of anti-inflammatory bacteria in the HD intervention group, including Alistipes putredinis, Akkermansia muciniphila, Bifidobacterium adolescentis, short-chain fatty acids (SCFAs)-producing bacterium Christensenella minuta, and secondary bile acids (SBAs)-producing bacterium Clostridium leptum. In the UC intervention group, the SCFA-producing bacterium Bacteroides stercoris, IBD-related bacterium Ruminococcus gnavus, Enterococcus faecalis, and the conditional pathogen Bacteroides caccae, were more abundant. Metabolomics analysis showed that the two types of FMT significantly modulated the metabolism of DSS-induced mice. Moreover, compared with the UC intervention group, indoleacetic acid and unsaturated fatty acids (DHA, DPA, and EPA) with anti-inflammatory effects were significantly enriched in the HD intervention group. In summary, these results indicate that FMT can alleviate the symptoms of colitis, and the effect of HD intervention is better than that of UC intervention. This study offers new insights into the mechanisms of FMT clinical intervention in IBD.

Impact of quorum sensing signaling molecules in gram-negative bacteria on host cells: current understanding and future perspectives.

Quorum sensing is a molecular signaling-based communication mechanism in prokaryotes. In the basic mode, signaling molecules released by certain bacteria are sensed by intracellular receptors or membrane-bound receptors of other members in the community, leading to the collective isogenic signaling molecule synthesis and synchronized activities. This regulation is important for the symbiosis of the bacterium with the host, as well as virulence and biofilm formation. Notably, quorum sensing signaling molecules are not only able to control microbial community behavior but can likewise regulate the physiological status of host cells. Here, we provide a comprehensive review of the importance of quorum sensing signaling molecules in gram-negative bacteria in regulating host cell function and gut health, and suggest possible opportunities for application in combating human and animal diseases by blocking the pathways through which quorum sensing signaling molecules exert their functions.

Intestinal Microbiota and Serum Metabolic Profile Responded to Two Nutritional Different Diets in Mice.

There is an interaction and bidirectional selection between dietary intake and gut microbiota due to the different efficiency of nutrients in the gut. The nutritional composition of germ-free (GF) diets differs significantly from specific pathogen-free (SPF) diets. There is, however, no data revealing how SPF animals from the same microbial background respond to them and if they affect the host. We examined the growth of SPF mice on the GF diet and found that it reduced body weight, intestinal length and intestinal morphology. Interestingly, the GF diet increased the level of pro-inflammatory bacteria in the gut of SPF mice, including Proteobacteria, Burkholderiaceae, Alloprevotella and Parasutterella. Furthermore, GF diets caused significant increases in malondialdehyde (MDA), IL-1ß, IL-6, and D-lactate levels in the serum of SPF mice and significantly altered their serum metabolic profile, especially amino acid metabolism. In conclusion, GF diets are not suitable for the growth and development of SPF mice. These findings, based on the role of gut microbiota in diet selection, provide new insights into the scientific and rational use of experimental animal diets.