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References: Fiber, Fatty Acids, and the Blood-Brain Barrier

  1. Fiber: MedlinePlus Medical Encyclopedia, US National Library of Medicine. A plain-language page on soluble and insoluble fiber, where each is found, how much fiber Americans eat (about 16 grams a day), and why adding fiber quickly can cause gas and bloating. The source for Section 6.2 and the At the Bedside case.

  2. From Dietary Fiber to Host Physiology: Short-Chain Fatty Acids as Key Bacterial Metabolites: Koh A, De Vadder F, Kovatcheva-Datchary P, Bäckhed F. Cell, 2016. A major review of how SCFAs act on receptors, block histone deacetylases, and serve as fuel. Advanced, but the abstract lays out the three ways SCFAs work in one paragraph.

  3. Short chain fatty acids in human large intestine, portal, hepatic and venous blood: Cummings JH, et al. Gut, 1987. The classic human autopsy study showing that fermentation happens mostly in the first part of the colon, that acetate is the main SCFA, and that the colon lining and liver take up butyrate and propionate. The numbers in Sections 6.3, 6.4, and the Read the Data question come from here.

  4. The microbiome and butyrate regulate energy metabolism and autophagy in the mammalian colon: Donohoe DR, et al. Cell Metabolism, 2011. Mouse study showing that colonocytes use bacterial butyrate as their main fuel and starve without it. A clear example of a germ-free mouse experiment.

  5. The Role of Short-Chain Fatty Acids From Gut Microbiota in Gut-Brain Communication: Silva YP, Bernardi A, Frozza RL. Frontiers in Endocrinology, 2020. A free, open-access review covering SCFA receptors (FFAR2 and FFAR3), gene effects, and the animal evidence on microglia and the blood-brain barrier. Good next reading for students who want more detail on Sections 6.6 and 6.10.

  6. Leaky gut: mechanisms, measurement and clinical implications in humans: Camilleri M. Gut, 2019. A review for doctors on what the gut barrier is, how permeability is measured in people, what raises it, and why public "leaky gut" claims need confirmation. The backbone of Sections 6.7 and 6.8.

  7. Serum zonulin as a marker of intestinal mucosal barrier function: May not be what it seems: Ajamian M, Steer D, Rosella G, Gibson PR. PLoS One, 2019. Open-access study showing that two commercial zonulin tests detected other blood proteins instead of zonulin. A useful example of checking whether a test measures what it claims.

  8. Metabolic endotoxemia initiates obesity and insulin resistance: Cani PD, et al. Diabetes, 2007. The mouse study that named metabolic endotoxemia, showing that a high-fat diet raised blood LPS and that LPS infusion caused metabolic changes in mice. Read it as mouse evidence only.

  9. Host microbiota constantly control maturation and function of microglia in the CNS: Erny D, et al. Nature Neuroscience, 2015. Mouse study finding that germ-free mice have immature microglia and that SCFAs and the FFAR2 receptor are involved. The source for microglia maturation in Section 6.10.

  10. The gut microbiota influences blood-brain barrier permeability in mice: Braniste V, et al. Science Translational Medicine, 2014. The germ-free mouse BBB study analyzed in this chapter's claim box. The full text lists group sizes, funders, and the butyrate experiments.

  11. Colon-delivered short-chain fatty acids attenuate the cortisol response to psychosocial stress in healthy men: Dalile B, et al. Neuropsychopharmacology, 2020. A small randomized, placebo-controlled trial in 66 healthy men, the closest human test of SCFAs and the stress system. It found a lower cortisol response but no change in mood.

  12. Role of anaerobic bacteria in the metabolic welfare of the colonic mucosa in man: Roediger WE. Gut, 1980. A classic lab study of colon-lining cells from human surgery specimens, showing that they burn butyrate as a main fuel. Free full text. Human cell evidence behind the Hype Meter card in Section 6.5.