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.
Fecal microbiota transplantation (FMT) is an emerging and effective therapy for the treatment of inflammatory bowel disease (IBD). Previous studies have reported that compared with FMT, whole intestinal microbiota transplantation (WIMT) can more precisely replicate the community structure and reduce the inflammatory response of the host. However, it remains unclear whether WIMT is more effective in alleviating IBD. To examine the efficacy of WIMT and FMT in the intervention of IBD, GF (Germ-free) BALB/c mice were pre-colonized with whole intestinal microbiota or fecal microbiota before being treated with dextran sodium sulfate (DSS). As expected, the symptoms of colitis were alleviated by both WIMT and FMT, as demonstrated by the prevention of body weight loss and decreased the Disease activity index and histological scores in mice. However, WIMT’s anti-inflammatory effect was superior to that of FMT. In addition, the inflammatory markers myeloperoxidase (MPO) and eosinophil peroxidase were dramatically downregulated by WIMT and FMT. Furthermore, the use of two different types of donors facilitated the regulation of cytokine homeostasis in colitis mice; the level of the pro-inflammatory cytokine IL-1β in the WIMT group was significantly lower than that in the FMT group, while the level of the anti-inflammatory factor IL-10 was significantly higher than that in the FMT group. Both groups showed enhanced expression of occludin to protect the intestinal barrier in comparison with the DSS group, and the WIMT group demonstrated considerably increased levels of ZO-1. The sequencing results showed that the WIMT group was highly enriched in Bifidobacterium, whereas the FMT group was significantly enriched in Lactobacillus and Ochrobactrum. Correlation analysis revealed that Bifidobacterium was negatively correlated with TNF-α, whereas Ochrobactrum was positively correlated with MPO and negatively correlated with IL-10, which might be related to different efficacies. Functional prediction using PICRUSt2 revealed that the FMT group was considerably enriched in the L-arginine biosynthesis I and L-arginine biosynthesis IV pathway, whereas the WIMT group was enriched in the L-lysine fermentation to acetate and butanoate pathway. In conclusion, the symptoms of colitis were subsided to varying degrees by the two different types of donors, with the WIMT group being more effective than the FMT group. This study provides new information on clinical interventions for IBD.
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.
Congestion is a natural phenomenon in core network, and is unavoidable if the queuing system is operated near capacity. Providing fairness among users with different levels of aggressiveness, and different levels of responsiveness is necessary for efficient network flow control. The scalability of current solutions depends on the number of active flows and the number of flows whose rate is greater that the current fair share. In this paper we propose a new fair active queue management scheme, called SDP (Selective Differentiated Penalization), that use the recent buffer resources allocation history to differentially penalize misbehaving flows by dropping more of their packets to make a tradeoff between scalability and fairness. The first principle of SDP is that the resulting throughput of each flow should be bounded by the max-min fair share bandwidth. The performance of SDP is aided by the fact that the recent history of buffer resource allocations can provide accurate rate estimates of active flow and the fair share threshold. Simulated results suggest that SDP provides a reasonable degree of max-min fair bandwidth allocation in a wide variety of operating conditions.
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