Nutritional Support from the Intestinal Microbiota Improves Hematopoietic Reconstitution after Bone Marrow Transplantation in Mice

Staffas, Anna; Silva, Marina Burgos da; Slingerland, Ann E.; Lazrak, Amina; Bare, Curtis J.; Holman, Corey D.; Docampo, Melissa D.; Shono, Yusuke; Durham, Benjamin H.; Pickard, Amanda J.; Cross, Justin R.; Stein‐Thoeringer, Christoph K.; Velardi, Enrico; Tsai, Jennifer J.; Jahn, Lorenz; Jay, Hillary; Lieberman, Sophie; Smith, Odette M.; Pamer, Eric G.; Peled, Jonathan U.; Cohen, David E.; Jenq, Robert R.; Brink, Marcel R.M. van den

doi:10.1016/j.chom.2018.03.002

Cited by 92 publications

(74 citation statements)

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“…Metabolic studies were performed as previously described in refs. [29][30][31]. Metabolic measurements were acquired through indirect calorimetry using the Promethion Metabolic Screening System (Sable Systems International, Las Vegas, NV, USA).…”

Section: Metabolic Measurement and Data Analysismentioning

confidence: 99%

Knockout of the X‐linkedFgf13in the hypothalamic paraventricular nucleus impairs sympathetic output to brown fat and causes obesity

et al. 2019

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Fibroblast growth factor (FGF)13, a nonsecreted, X‐linked, FGF homologous factor, is differentially expressed in adipocytes in response to diet, yet Fgf13′s role in metabolism has not been explored. Heterozygous Fgf13 knockouts fed normal chow and housed at 22°C showed hyperactivity accompanying reduced core temperature and obesity when housed at 30°C. Those heterozygous knockouts showed defects in thermogenesis even at 30°C and an inability to protect core temperature. Surprisingly, we detected trivial FGF13 in adipose of wild‐type mice fed normal chow and no obesity in adipose‐specific heterozygous knockouts housed at 30°C, and we detected an intact brown fat response through exogenous β3 agonist stimulation, suggesting a defect in sympathetic drive to brown adipose tissue. In contrast, hypothalamic‐specific ablation of Fgf13 recapitulated weight gain at 30°C. Norepinephrine turnover in brown fat was reduced at both housing temperatures. Thus, our data suggest that impaired CNS regulation of sympathetic activation of brown fat underlies obesity and thermogenesis in Fgf13 heterozygous knockouts fed normal chow.—Sinden, D. S., Holman, C. D., Bare, C. J., Sun, X., Gade, A. R., Cohen, D. E., Pitt, G. S. Knockout of the X‐linked Fgf13 in the hypothalamic paraventricular nucleus impairs sympathetic output to brown fat and causes obesity. FASEB J. 33, 11579–11594 (2019). http://www.fasebj.org

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Section: Metabolic Measurement and Data Analysismentioning

confidence: 99%

Knockout of the X‐linkedFgf13in the hypothalamic paraventricular nucleus impairs sympathetic output to brown fat and causes obesity

et al. 2019

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“…Alterations in the microbiome have been associated with clinical outcomes of patients who have undergone HCT, including their survival. However, the mechanisms by which the gut microbiota exerts its effects, both beneficial and detrimental, have not been fully elucidated [5, 6].…”

Section: Introductionmentioning

confidence: 99%

Monocyte reconstitution and gut microbiota composition after hematopoietic stem cell transplantation

Morjaria

Zhang

Kim

et al. 2019

Preprint

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Monocytes are an essential cellular component of the innate immune system that support the 33 host's effectiveness to combat a range of infectious pathogens. Hemopoietic cell transplantation (HCT) 34 results in transient monocyte depletion, but the factors that regulate recovery of monocyte populations 35 are not fully understood. In this study, we investigated whether the composition of the gastrointestinal 36 microbiota is associated with the recovery of monocyte homeostasis after HCT. 37 38 Methods: 39We performed a single-center, prospective, pilot study of 18 recipients of either autologous or 40 allogeneic HCT. Serial blood and stool samples were collected from each patient during their HCT 41 hospitalization. Analysis of the gut microbiota was done using 16S rRNA gene sequencing and flow 42 cytometric analysis was used to characterize the phenotypic composition of monocyte populations. 4344 Results: 45Dynamic fluctuations in monocyte reconstitution occurred after HCT and large differences were 46 observed in monocyte frequency among patients over time. Recovery of absolute monocyte counts and 47 monocyte subsets showed significant variability across the heterogeneous transplant types and 48 conditioning intensities; no relationship to the microbiota composition was observed in this small 49 cohort. 51 Conclusion: 52A relationship between the microbiota composition and monocyte homeostasis could not be 53 firmly established in this pilot study.3 54 55 cell transplantation (HCT) is a potentially curative procedure for patients with 81 hematologic malignancies but its success has been limited by the morbidity and mortality of post-82 transplant infections and relapse. Impaired immune reconstitution post-HCT increases the risk of both of 83 these complications [1][2][3][4]. Multiple factors influence the vulnerability of patients to these complications 84 including: time since transplantation, graft source (i.e., autologous (auto-HCT) or allogeneic (allo-HCT)), 85 and persisting myelosuppression (humoral and cell-mediated) post-HCT [2, 3]. Alterations in the 86 microbiome have been associated with clinical outcomes of patients who have undergone HCT, 87 including their survival. However, the mechanisms by which the gut microbiota exerts its effects, both 88 beneficial and detrimental, have not been fully elucidated [5, 6]. 89In humans there are three main circulating monocyte subsets with diverse functions, classified 90 based on their expression of CD14 and CD16 surface proteins and cytokine production. These monocyte 91 subsets are named "classical", "intermediate", and "non-classical monocytes" [7-9] and typically 92 comprise 85%, 10%, and 5% respectively of the circulating monocyte pool in a healthy individual under 93 homeostatic conditions [10, 11]. Classical monocytes specialize in phagocytosis and produce the 94 cytokine IL-10 [12], while intermediate monocytes have elevated surface expression of MHC class II, 95 suggesting they have an important role in antigen presentation [13]. In contrast, non-c...

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“…DNA from fecal pellets of individual mice were frozen until DNA was extracted by mechanical disruption (beadbeating) in phenol-chloroform. The V4-V5 region of the ribosomal RNA gene was amplified, sequenced, and computationally analyzed as described (36,37).…”

Section: Author Contributionsmentioning

confidence: 99%

Survival signal REG3α prevents crypt apoptosis to control acute gastrointestinal graft-versus-host disease

Zhao

Kim²,

Jeong

et al. 2018

Journal of Clinical Investigation

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Nutritional Support from the Intestinal Microbiota Improves Hematopoietic Reconstitution after Bone Marrow Transplantation in Mice

Cited by 92 publications

References 65 publications

Knockout of the X‐linkedFgf13in the hypothalamic paraventricular nucleus impairs sympathetic output to brown fat and causes obesity

Knockout of the X‐linkedFgf13in the hypothalamic paraventricular nucleus impairs sympathetic output to brown fat and causes obesity

Monocyte reconstitution and gut microbiota composition after hematopoietic stem cell transplantation

Survival signal REG3α prevents crypt apoptosis to control acute gastrointestinal graft-versus-host disease

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