Intestinal-derived FGF15 protects against deleterious effects of vertical sleeve gastrectomy in mice

Bozadjieva-Kramer, Nadejda; Shin, Jae Hoon; Shao, Yuchao; Gutiérrez-Aguilar, Ruth; Li, Ziru; Heppner, Kristy M.; Chiang, Samuel C.C.; Vargo, Sara G.; Granger, Katrina; Sandoval, Darleen A.; MacDougald, Ormond A.; Seeley, Randy J.

doi:10.1038/s41467-021-24914-y

Cited by 27 publications

(19 citation statements)

References 116 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Notable in mice that received SG was an expansion of Lactobacillus subspecies. We and others have consistently observed that SG led to considerable increases in the richness of Lactobacillus in obese rodents ( 22 , 23 , 43 ). These microbes are generally regarded as “healthy” bacteria and can be found in a variety of foods and probiotics which are often used to treat intestinal health issues ( 44 , 45 ).…”

Section: Discussionsupporting

confidence: 60%

“…Bariatric surgery has been reported to change the gut microbial populations ( 22 , 23 ), and alterations in the gut microbiota have been pointed as a potential modulator of the colonic inflammation observed in obesity ( 40 ). Therefore, we next characterized the intestinal bacterial changes following SG.…”

Section: Discussionmentioning

confidence: 99%

“…SG is currently one of the most effective treatments for obesity ( 19 ). Both human and rodent studies have recently indicated that SG can restore the disrupted gut microbiota resulting from HFD intake ( 20 , 21 ), with substantial rises in the abundance of multiple anti-inflammation bacteria such as Lactobacillus ( 22 , 23 ). Correspondingly, alterations of the intestinal bacteria following bariatric surgery are associated with improvements in the low-grade inflammation within different tissues such as liver and adipose tissue ( 24 , 25 ).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Sleeve gastrectomy decreases high-fat diet induced colonic pro-inflammatory status through the gut microbiota alterations

et al. 2023

Self Cite

View full text Add to dashboard Cite

BackgroundHigh-fat diet (HFD) induced obesity is characterized with chronic low-grade inflammation in various tissues and organs among which colon is the first to display pro-inflammatory features associated with alterations of the gut microbiota. Sleeve gastrectomy (SG) is currently one of the most effective treatments for obesity. Although studies reveal that SG results in decreased levels of inflammation in multiple tissues such as liver and adipose tissues, the effects of surgery on obesity related pro-inflammatory status in the colon and its relation to the microbial changes remain unknown.MethodsTo determine the effects of SG on the colonic pro-inflammatory condition and the gut microbiota, SG was performed on HFD-induced obese mice. To probe the causal relationship between alterations of the gut microbiota and improvements of pro-inflammatory status in the colon following SG, we applied broad-spectrum antibiotics cocktails on mice that received SG to disturb the gut microbial changes. The pro-inflammatory shifts in the colon were assessed based on morphology, macrophage infiltration and expressions of a variety of cytokine genes and tight junction protein genes. The gut microbiota alterations were analyzed using 16s rRNA sequencing. RNA sequencing of colon was conducted to further explore the role of the gut microbiota in amelioration of colonic pro-inflammation following SG at a transcriptional level.ResultsAlthough SG did not lead to pronounced changes of colonic morphology and macrophage infiltration in the colon, there were significant decreases in the expressions of several pro-inflammatory cytokines including interleukin-1β (IL-1β), IL-6, IL-18, and IL-23 as well as increased expressions of some tight junction proteins in the colon following SG, suggesting an improvement of pro-inflammatory status. This was accompanied by changing populations of the gut microbiota such as increased richness of Lactobacillus subspecies following SG. Importantly, oral administrations of broad-spectrum antibiotics to delete most intestinal bacteria abrogated surgical effects to relieve colonic pro-inflammation. This was further confirmed by transcriptional analysis of colon indicating that SG regulated inflammation related pathways in a manner that was gut microbiota relevant.ConclusionThese results support that SG decreases obesity related colonic pro-inflammatory status through the gut microbial alterations.

show abstract

Section: Discussionsupporting

confidence: 60%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Sleeve gastrectomy decreases high-fat diet induced colonic pro-inflammatory status through the gut microbiota alterations

et al. 2023

Self Cite

View full text Add to dashboard Cite

show abstract

“…Bozadjieva-Kramer et al (2021) performed vertical gastrectomy-induced osteopenia studies in intestinalspecific FGF15 null mice, revealing that intestinal FGF15 has positive effects on skeletal metabolism (30). The authors postulated that intestinal FGF15 protects against bone loss by restricting serum bile acid levels, but the role of the intestinal FXR-FGF15 axis and serum bile acids were not investigated (30). Appreciating that the FXR-FGF15 axis regulates endogenous intestinal FGF15 production, work by Bozadjieva-Kramer et al (2021) supports the concept that the intestinal FXR-FGF15 axis is a candidate regulator of bone metabolism.…”

Section: Introductionmentioning

confidence: 99%

“…Bozadjieva-Kramer et al performed vertical gastrectomy-induced osteopenia studies in intestinal specific FGF15-null mice, revealing that intestinal FGF15 has positive effects on skeletal metabolism ( 30 ). The authors postulated that intestinal FGF15 protects against bone loss by restricting serum bile acid levels, but the role of the intestinal FXR/FGF15 axis and serum bile acids were not investigated ( 30 ).…”

Section: Introductionmentioning

confidence: 99%

Minocycline-induced disruption of the intestinal FXR/FGF15 axis impairs osteogenesis in mice

et al. 2023

View full text Add to dashboard Cite

Antibiotic-induced shifts in the indigenous gut microbiota influence normal skeletal maturation. Current theory implies that gut microbiota actions on bone occur through a direct gut-bone signaling axis. However, our prior work supports that a gut-liver signaling axis contributes to gut microbiota effects on bone. Purpose was to investigate the effects of minocycline, a systemic antibiotic treatment for adolescent acne, on pubertal/postpubertal skeletal maturation. Sex-matched specific-pathogen-free(SPF) and germ-free(GF) C57BL/6T mice were administered a clinically relevant minocycline dose from age 6-12 weeks. Minocycline caused dysbiotic shifts in the gut bacteriome and impaired skeletal maturation in SPF mice, but did not alter the skeletal phenotype in GF mice. Minocycline administration in SPF mice disrupted the intestinal farnesoid X receptor(FXR)-fibroblast growth factor 15(FGF15) axis, a gut-liver endocrine axis supporting systemic bile acid homeostasis. Minocyclinetreated SPF mice had increased serum conjugated bile acids that are FXR antagonists, suppressed osteoblast function, decreased bone mass, impaired bone microarchitecture and fracture resistance. Stimulating osteoblasts with the serum bile acid profile from minocycline-treated SPF mice recapitulated the suppressed osteogenic phenotype found in vivo, which was mediated through attenuated FXR-signaling. This work introduces bile acids as a novel mediator of gut-liver signaling actions contributing to gut microbiota effects on bone.

show abstract

The Genetic and Microbial Influences in Obesity and Obesity Management

Suh,

Kindel

2024

The SAGES Manual of Metabolic and Bariatric Surgery

View full text Add to dashboard Cite

Intestinal-derived FGF15 protects against deleterious effects of vertical sleeve gastrectomy in mice

Cited by 27 publications

References 116 publications

Sleeve gastrectomy decreases high-fat diet induced colonic pro-inflammatory status through the gut microbiota alterations

Sleeve gastrectomy decreases high-fat diet induced colonic pro-inflammatory status through the gut microbiota alterations

Minocycline-induced disruption of the intestinal FXR/FGF15 axis impairs osteogenesis in mice

The Genetic and Microbial Influences in Obesity and Obesity Management

Contact Info

Product

Resources

About