Gut microbiota–dependent modulation of innate immunity and lymph node remodeling affects cardiac allograft outcomes

Bromberg, Jonathan S.; Hittle, Lauren E.; Xiong, Yanbao; Saxena, Vikas; Smyth, Eoghan M.; Li, Lushen; Wagner, Chelsea; Fricke, W. Florian; Thézenas, Simon; Brinkman, C. Colin; Mongodin, Emmanuel F.

doi:10.1172/jci.insight.142528

Cited by 22 publications

(55 citation statements)

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“…Animal studies revealed that isogenic rodents, which differ in their gut microbial composition, show distinct allograft rejection kinetics 46,47 . Although the underlying mechanisms remain elusive, it was suggested that certain Proteobacteria induce a pro‐inflammatory state linked to allograft rejection 48 . In contrast, Bifidobacterium pseudolongum strains decrease pro‐inflammatory cytokine levels such as IL‐6 and TNF‐α while increasing IL‐10 levels, which generally inhibits immune activation 48 .…”

Section: Clinical Implications Of Dysbiosis In Sotmentioning

confidence: 99%

“…Although the underlying mechanisms remain elusive, it was suggested that certain Proteobacteria induce a pro‐inflammatory state linked to allograft rejection 48 . In contrast, Bifidobacterium pseudolongum strains decrease pro‐inflammatory cytokine levels such as IL‐6 and TNF‐α while increasing IL‐10 levels, which generally inhibits immune activation 48 . Clinical findings about the role of the gut microbiome in solid organ transplant rejection are limited.…”

Section: Clinical Implications Of Dysbiosis In Sotmentioning

confidence: 99%

“…In HSCT, a pilot study evaluating the impact of Lactobacillus rhamnosus on GvHD incidence is currently underway (NCT02144701, see Table 2). In SOT, results are limited to pre‐clinical intervention studies, in which the administration of certain commensal bacteria or probiotics reduced allograft immunity 48 and alleviated immunosuppressant toxicity in mice 78 . Probiotics can be administered as monostrain (only one bacteria) or multistrain (cocktail of different bacteria) products and can be derived from empiric evidence (traditional probiotics) or isolated from the gut after proving their beneficial effect in microbiome studies (next‐generation probiotics).…”

Section: Microbiome‐targeted Therapeutic Interventionsmentioning

confidence: 99%

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The gut microbiome in solid organ transplantation

Arassi

Zeller

Karcher

et al. 2020

Pediatric Transplantation

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Allogeneic transplantation is an important, albeit rarely curative therapy for a large number of end-stage organ diseases and haematopoietic disorders. The introduction of potent immunosuppressants and anti-infective prophylaxis has continuously and substantially improved transplant outcome and patient survival. However, rejections, infections, and immunosuppressant-specific adverse effects remain a serious threat to allograft function and patient health. Therefore, innovative and individualized therapeutic interventions to alleviate treatment toxicity and improve patient mortality remain an unmet need. This is particularly pressing in paediatric patients, for whom transplant-related complications are more frequent than for adults and transplant dysfunction is more detrimental due to children's longer life expectancy and dependence on a functioning graft. Recently, accumulating evidence has suggested the human

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Section: Clinical Implications Of Dysbiosis In Sotmentioning

confidence: 99%

Section: Clinical Implications Of Dysbiosis In Sotmentioning

confidence: 99%

Section: Microbiome‐targeted Therapeutic Interventionsmentioning

confidence: 99%

See 1 more Smart Citation

The gut microbiome in solid organ transplantation

Arassi

Zeller

Karcher

et al. 2020

Pediatric Transplantation

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“…The microbiome analysis followed previously‐described procedures (Bromberg et al, 2018). Briefly, DNA samples were isolated from antibody‐injected engorged nymphs (3 ticks/group).…”

Section: Methodsmentioning

confidence: 99%

“…PCR amplification was performed, targeting the V3V4 hypervariable region of the 16S rRNA gene, followed by sequencing on the Illumina HiSeq 2500 platform (San Diego, CA). After sequencing, 16S rRNA reads were processed and analysed using the QIIME software package, as in published methods (Bromberg et al, 2018).…”

Section: Methodsmentioning

confidence: 99%

A novel tick protein supports integrity of gut peritrophic matrix impacting existence of gut microbiome and Lyme disease pathogens

Yang

Koči

Smith

et al. 2020

Cellular Microbiology

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The peritrophic matrix (PM) is an acellular membrane that covers the gut epithelium in arthropods and physically separates it from the lumen. The structure is thought to play an important role in tick biology. The PM is also known to impact the persistence of tick‐borne pathogens like Borrelia burgdorferi, although limited information is available about its molecular constituents or their biological significance. Herein, we characterise a novel PM‐associated gut protein in Ixodes scapularis ticks, annotated as Peritrophic Membrane Chitin Binding Protein (PM_CBP), for its role in the integrity and function of the matrix. The PM_CBP displays homology to the chitin deacetylase metalloenzyme, shows upregulation during tick feeding, and is localized at the luminal surface of the gut epithelium. The structural integrity of the PM was impaired both by the knock down of PM_CBP expression via RNA interference and by treatment with anti‐PM_CBP antibodies, as revealed by its electron microscopic appearance. Additionally, the duration of tick engorgement on mice and the passage of experimentally‐inoculated fluorescent dextran molecules across the PM are affected by the knock down of PM_CBP expression. The transfer of anti‐PM_CBP antibodies into the tick gut impacted the overall composition of the resident microbiome, and also influenced B. burgdorferi acquisition in ticks and its transmission to mice. Taken together, these data highlight the biological significance of the Ixodes PM and suggest that the targeting of its molecular constituents may contribute to the development of novel interventions against tick‐borne infections.

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Colitis-Induced Microbial Perturbation Promotes Postinflammatory Visceral Hypersensitivity

Esquerre

Basso

Defaye

et al. 2020

Cellular and Molecular Gastroenterology and Hepatology

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Our understanding of the pathophysiological mechanisms underlying chronic pain in inflammatory bowel disease is incomplete. Here we show that microbial manipulation modulates the development of visceral, but not somatic, pain in a mouse model of postinflammatory dextran sodium sulfate colitis. CONCLUSIONS:The microbiome plays a central role in postinflammatory visceral hypersensitivity. Microbial-derived SCFAs can sensitize nociceptive neurons and may contribute to the pathogenesis of postinflammatory visceral pain.

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Gut microbiota–dependent modulation of innate immunity and lymph node remodeling affects cardiac allograft outcomes

Cited by 22 publications

References 0 publications

The gut microbiome in solid organ transplantation

The gut microbiome in solid organ transplantation

A novel tick protein supports integrity of gut peritrophic matrix impacting existence of gut microbiome and Lyme disease pathogens

Colitis-Induced Microbial Perturbation Promotes Postinflammatory Visceral Hypersensitivity

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