Gut microbiota–dependent modulation of innate immunity and lymph node remodeling affects cardiac allograft outcomes
Jonathan S. Bromberg,Lauren E. Hittle,Yanbao Xiong,Vikas Saxena,Eoghan M. Smyth,Lushen Li,Tianshu Zhang,Chelsea Wagner,W. Florian Fricke,Thomas Simon,C. Colin Brinkman,Emmanuel F. Mongodin +11 more
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TLDR
Analysis of mesenteric and peripheral lymph node structure showed that B. pseudolongum gavage resulted in a higher laminin α4/α5 ratio in the lymph node cortical ridge, indicative of a suppressive environment, while D. desulfuricans results in a lower lamination ratio, supportive of inflammation.Abstract:
We hypothesized that the gut microbiota influences survival of murine cardiac allografts through modulation of immunity. Antibiotic pretreated mice received vascularized cardiac allografts and fecal microbiota transfer (FMT), along with tacrolimus immunosuppression. FMT source samples were from normal, pregnant (immune suppressed), or spontaneously colitic (inflammation) mice. Bifidobacterium pseudolongum (B. pseudolongum) in pregnant FMT recipients was associated with prolonged allograft survival and lower inflammation and fibrosis, while normal or colitic FMT resulted in inferior survival and worse histology. Transfer of B. pseudolongum alone resulted in reduced inflammation and fibrosis. Stimulation of DC and macrophage lines with B. pseudolongum induced the antiinflammatory cytokine IL-10 and homeostatic chemokine CCL19 but induced lesser amounts of the proinflammatory cytokines TNFα and IL-6. In contrast, LPS and Desulfovibrio desulfuricans (D. desulfuricans), more abundant in colitic FMT, induced a more inflammatory cytokine response. Analysis of mesenteric and peripheral lymph node structure showed that B. pseudolongum gavage resulted in a higher laminin α4/α5 ratio in the lymph node cortical ridge, indicative of a suppressive environment, while D. desulfuricans resulted in a lower laminin α4/α5 ratio, supportive of inflammation. Discrete gut bacterial species alter immunity and may predict graft outcomes through stimulation of myeloid cells and shifts in lymph node structure and permissiveness.read more
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Gut Immune Maturation Depends Upon Colonization with Host-Specific Microbiota
TL;DR: In this paper, the authors colonized GF mice with mouse microbiota (MMb) or human microbiota (HMb) to determine whether small intestinal immune maturation depends on a coevolved host-specific microbiota.
Journal ArticleDOI
Cytokine Research in Depression: Principles, Challenges, and Open Questions.
Hubertus Himmerich,Hubertus Himmerich,Olivia Patsalos,Nicole Lichtblau,Mohammad A. A. Ibrahim,Bethan Dalton +5 more
TL;DR: Cytokines might not be associated with the diagnosis of depression according to the currently used diagnostic manuals, but rather with specific subtypes of depression, or with depressive symptoms across different psychiatric diagnoses, therefore the currently available diagnostic systems may not be the ideal starting point for psychiatric cytokine research.
Journal ArticleDOI
The probiotic L. casei Zhang slows the progression of acute and chronic kidney disease
Han Zhu,Chujin Cao,Wu Zhongcai,Heping Zhang,Sun Zhihong,Min Wang,Huzi Xu,Zhi Zhao,Yuxi Wang,Guangchang Pei,Qian Yang,Fengming Zhu,Juan Yang,Xuan Deng,Yu Hong,Yinzheng Li,Jie Sun,Fan Zhu,Mengxia Shi,Kun Qian,Ting Ye,Xuezhi Zuo,Fenfei Zhao,Jing Guo,Gang Xu,Ying Yao,Rui Zeng +26 more
TL;DR: This article showed that probiotic Lactobacillus casei Zhang (L.casei Zhang) corrected bilateral renal ischemia-reperfusion (I/R)-induced gut microbial dysbiosis, alleviated kidney injury, and delayed its progression to CKD in mice.
Journal ArticleDOI
Antibiotic pretreatment alleviates liver transplant damage in mice and humans
Kojiro Nakamura,Shoichi Kageyama,Takahiro Ito,Hirofumi Hirao,Kentaro Kadono,Antony Aziz,Kenneth J. Dery,Matthew J Everly,Kojiro Taura,Shinji Uemoto,Douglas G. Farmer,Fady M. Kaldas,Ronald W. Busuttil,Jerzy W. Kupiec-Weglinski +13 more
TL;DR: This study documents the benefits of Abx pretreatment in liver transplant recipients, identifies ER stress and autophagy regulation by the PGE2/EP4 axis as a homeostatic underpinning, and points to the microbiome as a therapeutic target in OLT.
Journal ArticleDOI
Gut Microbial Metabolites Induce Donor-Specific Tolerance of Kidney Allografts through Induction of T Regulatory Cells by Short-Chain Fatty Acids.
Huiling Wu,Huiling Wu,Julian Singer,Tony Kwan,Yik Wen Loh,Chuanmin Wang,Jian Tan,Yan Li,Sum Wing Christina Lai,Laurence Macia,Stephen I. Alexander,Stephen I. Alexander,Steven J. Chadban,Steven J. Chadban +13 more
TL;DR: Diet-based therapy to induce changes in the gut microbiome can alter systemic alloimmunity in mice, in part through the production of short-chain fatty acids leading to Treg cell development, and merits study as a potential clinical strategy to facilitate transplant acceptance.
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