Bariatric surgery is currently one of the most effective interventions to treat obesity. The gut microbiome regulates host metabolism and adiposity and some researchers have shown that the surgically altered microbiome may contribute reducing adiposity in patients after Roux-en-Y gastric bypass (RYGB).
Recent findings have also revealed a glycemic improvement of patients with type 2 diabetes after RYGB, while it is plausible that other mechanisms are involved in the weight loss.
A new study, led by Dan Linetzky Waitzberg from Universidade de São Paulo, shows that reduced red meat intake, plasma indole-3-acetate, and Dorea longicatena are associated with better insulin resistance in women with type 2 diabetes and obesity after RYGB surgery.
RYGB improved glycemic control biomarkers including fasting blood glucose, glycated hemoglobin, insulin, and the Homeostasis Assessment Model, the latter considered a method for assessing beta-cell function and insulin resistance.
At the gut microbiome level, RYGB affected the gut microbiota composition -3 bacterial taxa were reduced and 24 increased three months after RYGB- without changes in overall alpha diversity. Moreover, gastric bypass promoted changes in the three major tryptophan metabolic pathways (the indole pathway in bacteria and the kynurenine and serotonin pathways in mammalian cells), as reported by changes in plasma tryptophan metabolites N-acetyl-serotonin, indole-3-acetate, and anthranilic acid. With regards to food intake, the greater the reduction in red meat intake and the smaller the reduction in protein intake after RYGB, the better the insulin resistance after surgery.
When exploring all variables together, the authors found that a reduction in red meat intake, an increase in plasma indole-3-acetate, and an increase in Dorea longicatena correlated with most improvements of insulin resistance after surgery. In particular, D. longicatena is a producer of indole-3-acetate that is a known gut microbial metabolite involved in reducing inflammation and insulin resistance by stimulating insulin secretion.
Metabolic disorders are associated with alterations in the composition and function of the gut microbiota, with short-chain fatty acids, branched-chain amino acids, trimethylamine N-oxide, and tryptophan and indole derivatives emerging as potential biomarkers for early diagnosis and promising targets for interventions in cases of obesity and related metabolic disorders.
Previous research also showed that tryptophan metabolites produced by host and gut microbiota can lead to improving type 2 diabetes after RYGB. The authors hypothesized that a preference for milk and eggs instead of red meat after surgery would shift the gut microbiota composition towards a less pro-inflammatory profile that could explain the better insulin resistance associated with reduced red meat intake and protein intake.
Altogether, these findings provide new insights into the role of food intake, tryptophan metabolism, and gut microbiota composition on the improved glycemic control observed in certain patients with type 2 diabetes after bariatric surgery. The durability of the benefits provided by gastric bypass surgery could be at stake. As a result, the study of gut microbiota signatures in patients with obesity and/or type 2 diabetes might pave the way for using gut microbiota composition and function as a marker to help clinicians when deciding whether to recommend bariatric surgery, although potential applications of emerging microbiome tests are not yet ready for use in routine clinical practice.
References:
Tremaroli V, Karlsson F, Werling M, et al. Roux-en-Y gastric bypass and vertical banded gastroplasty induce long-term changes on the human gut microbiome contributing to fat mass regulation. Cell Metab. 2015; 22(2):228-238. doi: 10.1016/j.cmet.2015.07.009.
Aguiar Prudêncio AP, Fonseca DC, Mendonça Machado N, et al. Red meat intake, indole-3-acetate, and Dorea longicatena together affect insulin resistance after gastric bypass. Nutrients. 2023; 15(5):1185. doi: 10.3390/nu15051185.
Agus A, Clément K, Sokol H. Gut microbiota-derived metabolites as central regulators in metabolic disorders. Gut. 2021; 70(6):1174-1182. doi: 10.1136/gutjnl-2020-323071.
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