lucy-mailing-ppar-γ-pathway-oxygen-hypothesis-reversing-gut-dysbiosis-actionable-items.md

lucy-mailing-ppar-γ-pathway-oxygen-hypothesis-reversing-gut-dysbiosis-actionable-items.md

• Reversing gut dysbiosis
  Butyrate (tributyrin) supplementation

  • Antibiotics wipe out butyrate producers, putting significant stress on the cells that line the large intestine. If we can support epithelial metabolism with supplemental butyrate until our butyrate-producers can recover, theoretically, we may be able to prevent an environment that favors opportunistic pathogens.
  Glutamine supplementation

  • (Likewise, supplementing with glutamine may prevent antibiotic-induced dysbiosis in the small intestine.)
  targeting PPAR-gamma and colonic energy starvation

  • Mesalamine (5-ASA): this drug is commonly used as first-line treatment of IBD. It’s anti-inflammatory effects have been shown to be mediated through its ability to upregulate PPARgamma.23
  • Danshensu Bingpian Zhi (DBZ): this compound is derived from tanshinol and borneol, found in the traditional Chinese medicinal formula Fufang Danshen. It upregulates PPAR-gamma, and has demonstrated potential for attenuating dysbiosis.25 Note: *Herbals should be sourced and dosed carefully, ideally under the direction of a physician experienced in herbal medicine.*
  • Butyrate: a short-chain fatty acid and potent stimulator of PPAR-gamma. Even low concentrations of butyrate have been shown to increase PPAR-gamma protein expression by 7-fold*.* *I typically recommend** *[*ProButyrate*](https://www.tessmed.com/product/probutyrate/)*, though *[*ButyCaps Tributyrin*](https://www.laboratoire-optim.com/en/butycaps/)* may also be a viable option (no affiliations).*
  • Ketones: beta-hydroxybutyrate and acetoacetate almost certainly activate PPAR-gamma in intestinal epithelial cells, just as butyrate does. A ketogenic diet has been shown to upregulate PPAR-gamma across a number of tissues and also provides substrate for beta oxidation and epithelial energy production. *I am hoping to support more research in this area.*
  • Fasting/caloric restriction: One study found that intestinal PPAR-gamma was required for sympathetic nervous system activation during caloric restriction.27 However, the degree to which fasting or caloric restriction induces this pathway in the gut is still unclear.
  • Exercise: one research group found that the protective effects of voluntary exercise on the gut in both a colitis model and a diet-induced obesity model were mediated by the ability of exercise to increase endogenous glucocorticoids in the gut and upregulate PPAR-gamma!28,29 *Future studies in our lab will be studying the potential implications of exercise on this pathway.*
  • Stress management: stress reduces PPAR-gamma expression in the gut.20
  • Cannabinoids: cannabidiol (CBD) reduced iNOS activity in rectal biopsies of patients with ulcerative colitis, an effect that was mediated through activation of PPAR-gamma.30
  • Sulforaphane: a 2008 found that this phytochemical from cruciferous vegetables enhances components of innate immunity via activation of PPAR-gamma.31
  • Curcumin: one study found that curcumin inhibited chemically-induced colitis in mice by activation of PPAR-gamma.32 The oral dosage required to achieve these effects is unknown.
  • Other herbals: chamomile, angelica, silymarin, licorice root, and lemon balm are all partial activators of PPAR-gamma. These herbs can be taken individually but are all found within the product [Iberogast](https://www.iberogast.com/), which has been shown to be clinically effective for IBS and functional GI disorders.33
  • Fatty acids: Conjugated linoleic acid (CLA)34 and omega-3 fatty acids (DHA)35 both enhance expression of PPAR-gamma.
  • Probiotics: *In vitro* studies on colonocytes have demonstrated the ability of Saccharomyces boulardii to increase PPAR-gamma expression.
  • Prebiotics: *in vitro* studies on colonocytes have shown that the anti-inflammatory effects of the oligosaccharides alpha3-siallylactose and FOS are mediated through their ability to induce PPAR-gamma.36
  • Vitamin A: retinoic acid, a form of vitamin A, is required for the activation and function of PPAR-gamma.
  - Source: [The oxygen-gut dysbiosis connection: How to break the cycle of gut inflammation, dysbiosis, and epithelial energy starvation](https://www.lucymailing.com/the-oxygen-gut-dysbiosis-connection/)