Gut microbiome influences bone remodeling after gastric bypass
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Changes in the human gut microbiome after sleeve gastrectomy contribute to the negative skeletal impact of bariatric surgery among adults with obesity, according to a speaker.
“Gut bacteria are increasingly recognized as playing an important role in modulating host functions, and studies have suggested a link between the gut and bone,” Karin Wu, MD, a fellow in the Benioff Center for Microbiome Medicine at the University of California, San Francisco, said during an online presentation at the virtual American Society for Bone and Mineral Research Annual Meeting. “In animal models, alterations in the gut microbiome result in a differential bone phenotype, suggesting that the contents of the gut influence bone mass.”
The mechanisms behind how the gut bacteria affect bone are not fully defined, but seem to be mediated in part by the metabolites individual bacteria produce, Wu said.
“When we ingest dietary fiber, our gut microbes ferment it to produce short-chain fatty acids,” Wu said. “Short-chain fatty acids, particularly butyrate, have been shown to affect bone homeostasis. First, they directly influence metabolic reprogramming of osteoclast precursors, and therefore inhibit osteoclastogenesis. They have also been shown to modulate the immune system, influence calcium absorption and affect endocrine functions such as [insulin-like growth factor] I production.”
These changes could be further enhanced after bariatric surgery, which has also been shown to affect the gut microbiome, Wu said.
“Meanwhile, bariatric surgery has the unintended consequence of inducing abnormalities in bone metabolism,” Wu said.
In an exploratory, longitudinal, observational study, Wu and colleagues assessed adults with obesity who underwent sleeve gastrectomy at baseline (1 month before surgery; n = 22) and 6 months after surgery (n = 15; mean age, 50 years; 82% women; 64% white; mean baseline BMI, 45 kg/m²). Researchers analyzed serum bone turnover markers, fractional calcium absorption, dietary intake and stool samples for microbial composition for all participants.
At 6 months after surgery, participants experienced an average of 28 kg weight loss (P < .001). C-terminal telopeptide of type 1 collagen increased by a mean of 229% (P < .01) and procollagen type 1 N-terminal propeptide (P1NP) increased by a mean of 68% (P < .001). At 6 months, mean areal bone mineral density decreased by –4.4% at the femoral neck (P = .003), –5.2% at the total hip (P < .001) and remained unchanged at the lumbar spine.
Researchers found that higher alpha diversity of gut bacteria — or the change in number of gut species within each stool sample — was associated with higher bone turnover marker measurements 6 months after surgery.
“This indicates that the greater the number of bacterial types observed in the sample, the higher the bone turnover markers,” Wu said.
Additionally, a greater increase in alpha diversity protected participants from femoral neck BMD loss after surgery, Wu said. Data at 6 months showed that P1NP levels were higher among participants with a greater change in gut microbial composition, Wu said.
Stool analyses also showed that butyrate metabolism decreased at 6 months after surgery (P = .043).
“We can conclude that sleeve gastrectomy-induced alterations in the gut microbiome may influence skeletal outcomes,” Wu said. “This is a hypothesis-generating study.”
Wu said researchers plan to analyze the cohort at 12 months after surgery and assess other bone outcomes.
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Wu K, et al. Role of the gut microbiome in bone metabolism in severe obesity and after sleeve gastrectomy. Presented at: American Society for Bone and Mineral Research Annual Meeting; Sept. 11-15, 2020 (virtual meeting).
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