TLR2 and interleukin-10 are involved in Bacteroides fragilis-mediated prevention of DSS-induced colitis in gnotobiotic mice

Chang, Yi-Chih; Ching, Yung-Hao; Chiu, Chien-Chao; Liu, Ju-Yun; Hung, Shao-Wen; Huang, Wen-Ching; Huang, Yen-Te; Chuang, Hsiao-Li

doi:10.1371/journal.pone.0180025

Cited by 92 publications

(56 citation statements)

References 38 publications

(47 reference statements)

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“…IL‐10 is a prototypical anti‐inflammatory cytokine which inhibits the synthesis of pro‐inflammatory cytokines such as TNF‐ɑ and IFN‐Ɣ thus limiting pathological cell shedding responses 30 . IL‐10 induction has previously been described to be driven by certain microbiota members such as Bacteroides , Bifidobacterium and Helicobacter , suggesting that specific members may play a key role for inducing anti‐inflammatory and anti‐apoptotic responses, thereby driving protective barrier integrity during the neonatal period 31-34 …”

Section: Discussionmentioning

confidence: 99%

The early life microbiota protects neonatal mice from pathological small intestinal epithelial cell shedding

et al. 2020

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The early life gut microbiota plays a crucial role in regulating and maintaining the intestinal barrier, with disturbances in these communities linked to dysregulated renewal and replenishment of intestinal epithelial cells. Here we sought to determine pathological cell shedding outcomes throughout the postnatal developmental period, and which host and microbial factors mediate these responses. Surprisingly, neonatal mice (Day 14 and 21) were highly refractory to induction of cell shedding after intraperitoneal administration of liposaccharide (LPS), with Day 29 mice showing strong pathological responses, more similar to those observed in adult mice. These differential responses were not linked to defects in the cellular mechanisms and pathways known to regulate cell shedding responses. When we profiled microbiota and metabolites, we observed significant alterations. Neonatal mice had high relative abundances of Streptococcus, Escherichia, and Enterococcus and increased primary bile acids. In contrast, older mice were dominated by Candidatus Arthromitus, Alistipes, and Lachnoclostridium, and had increased concentrations of SCFAs and methyamines. Antibiotic treatment of neonates restored LPS-induced small intestinal cell shedding, whereas adult fecal microbiota transplant alone had no effect.Our findings further support the importance of the early life window for microbiotaepithelial interactions in the presence of inflammatory stimuli and highlights areas for further investigation. K E Y W O R D S antibiotics, cell shedding, early life, fecal microbiota transplant, inflammation, intestinal epithelium, metabolites, microbiota 7076 | HUGHES Et al.

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Section: Discussionmentioning

confidence: 99%

The early life microbiota protects neonatal mice from pathological small intestinal epithelial cell shedding

et al. 2020

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“…IL-10 is a prototypical anti-inflammatory cytokine which inhibits the synthesis of pro-inflammatory cytokines such as TNF-ɑ and IFN-Ɣ thus limiting pathological cell shedding responses [23]. IL-10 induction has previously been described to be driven by certain microbiota members such as Bacteroides, Bifidobacterium and Helicobacter, suggesting that specific members may play a key role for inducing anti-inflammatory and anti-apoptotic responses, thereby driving protective barrier integrity during the neonatal period [24][25][26][27].…”

Section: Discussionmentioning

confidence: 99%

The early life microbiota protects neonatal mice from pathological small intestinal epithelial cell shedding

Hughes

Schofield

Dalby

et al. 2019

Preprint

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AbstractThe gut microbiota plays a crucial role in regulating and maintaining the epithelial barrier, particularly during early life. Notably, patients with chronic intestinal inflammation have a dysregulated process of renewal and replenishment of the intestinal epithelial cell (IEC) barrier, which is linked to disturbances in the gut microbiota. To date, there are no studies focussed on understanding the impact of inflammatory cell shedding events during the early life developmental window, and which host and microbial factors mediate these responses. Here we sought to determine pathological cell shedding outcomes throughout the postnatal developmental period (day 14, 21, 29 and week 8). Surprisingly neonatal mice (day 14 and 21) were highly refractory to induction of cell shedding after intraperitoneal administration of LPS, with day 29 mice showing strong pathological responses, more similar to those observed in adult mice. These differential responses were not linked to defects in the cellular mechanisms and pathways known to regulate cell shedding responses, although we did observe that neonatal mice had elevated anti-inflammatory (IL-10) responses. Notably, when we profiled microbiota and metabolites from these mice, we observed significant alterations. Neonatal mice had high relative abundances of Streptococcus, Escherichia and Enterococcus and increased primary bile acids. In contrast, older mice were dominated by Candidatus Arthromitus, Alistipes and Lachnoclostridium, and had increased concentrations of SCFAs and methyamines. Faecal microbiota transplant (FMT) and antibiotic studies confirmed the importance of early life gut microbiota in cell shedding responses. In these studies, neonates treated with antibiotics restored LPS-induced small intestinal cell shedding, whereas adult FMT alone had no effect. Our findings further support the importance of the early life window for microbiota-epithelial interactions in the presence of inflammatory stimuli and highlight areas for further investigation to probe underlying mechanisms to drive therapeutic development within the context of chronic inflammatory intestinal diseases.

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“…For instance, Bacteroides fragilis contains capsular polysaccharide A, which can activate FoxP3 + CD4 + Tregs in the lamina propria by up-regulating the inhibitory cytokine, IL-10; which subsequently activates the TLR2 signaling pathway. Further, B. fragilis may alter the Treg/Th17 balance by counteracting the inflammatory response induced by LPS, thereby exerting an immunomodulatory effect (71).…”

Section: Relationship Between Intestinal Flora Regional Immune Regulmentioning

confidence: 99%

Intestinal Flora and Disease Mutually Shape the Regional Immune System in the Intestinal Tract

et al. 2020

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The intestinal tract is the largest digestive organ in the human body. It is colonized by, and consistently exposed to, a myriad of microorganisms, including bifidobacteria, lactobacillus, Escherichia coli, enterococcus, clostridium perfringens, and pseudomonas. To protect the body from potential pathogens, the intestinal tract has evolved regional immune characteristics. These characteristics are defined by its unique structure, function, and microenvironment, which differ drastically from those of the common central and peripheral immune organs. The intestinal microenvironment created by the intestinal flora and its products significantly affects the immune function of the region. In turn, specific diseases regulate and influence the composition of the intestinal flora. A constant interplay occurs between the intestinal flora and immune system. Further, the intestinal microenvironment can be reconstructed by probiotic use or microbiota transplantation, functioning to recalibrate the immune homeostasis, while also contributing to the treatment or amelioration of diseases. In this review, we summarize the relationship between the intestinal flora and the occurrence and development of diseases as an in-turn effect on intestinal immunity. We also discuss improved immune function as it relates to non-specific and specific immunity. Further, we discuss the proliferation, differentiation and secretion of immune cells, within the intestinal region following remodeling of the microenvironment as a means to ameliorate and treat diseases. Finally, we suggest strategies for improved utilization of intestinal flora.

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TLR2 and interleukin-10 are involved in Bacteroides fragilis-mediated prevention of DSS-induced colitis in gnotobiotic mice

Cited by 92 publications

References 38 publications

The early life microbiota protects neonatal mice from pathological small intestinal epithelial cell shedding

The early life microbiota protects neonatal mice from pathological small intestinal epithelial cell shedding

The early life microbiota protects neonatal mice from pathological small intestinal epithelial cell shedding

Intestinal Flora and Disease Mutually Shape the Regional Immune System in the Intestinal Tract

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