Digestive Diseases Research

Kaunitz Laboratory

Jonathan D. Kaunitz, MD

Key investigators

  • Jonathan D. Kaunitz, MD
  • Yasutada Akiba, MD, PhD

Funding

  • VA Merit
  • Shire Pharmaceuticals

Current research projects

  • Mechanisms of endotoxin uptake from the gut
  • Prevention of acute pancreatitis complications
  • Targeted treatment of metabolic disease

Future research directions

  • Metabolite activation of gut chemosensory mechanisms in the treatment of acute and chronic endotoxin-related disease
  • Novel treatments for IBS
  • Novel treatments for secretory diarrhea

Awards

  • 16th Annual Hans H. Ussing Lecture (April 2024)
    • Dr. Kaunitz, professor of medicine in the Vatche & Tamar Manoukian Division of Digestive Diseases and senior clinician-scientist investigator at the VA Greater Los Angeles Healthcare System, joined a long list of distinguished scientists in giving the Hans H. Ussing lecture at the 2024 American Physiological Society (APS) Summit Meeting. Of the 16 awardees, Dr. Kaunitz is one of only three gastroenterologists and seven physicians to receive this national award for outstanding contributions to fundamental research in epithelial transport. In his lecture, Dr. Kaunitz recounted his research fellowship at UCLA in the laboratory of Ernest Wright in the early 1980s, when he studied the kinetics of sodium-glucose cotransport, building on Dr, Wright’s work and culminating in the cloning of the intestinal sodium-glucose cotransporter, laying the groundwork for the development of the SGLT2 inhibitors used to treat diabetes and oral rehydration solutions used to treat cholera. 

Key publications - Full list on PubMed

  1. Hollander D, Kaunitz JD. The “Leaky Gut”: Tight Junctions but Loose Associations? Digestive Diseases and Sciences (2020) 65:1277–1287 https://doi.org/10.1007/s10620-019-05777-2. Editorial.
  2. Bhattarai Y, Williams BB, Battaglioli EJ, Whitaker WR, Till L, Grover M, Linden DR, Akiba Y, Kandimalla KK, Zachos NC, Kaunitz JD, Sonnenburg JL, Fischbach MA, Farrugia G, Kashyap PC. Gut Microbiota-Produced Tryptamine Activates an Epithelial G-Protein-Coupled Receptor to Increase Colonic Secretion. Cell Host Microbe. 2018 Jun 13;23(6):775-785.e5
  3. Kaji I, Akiba Y, Furuyama T, Adelson DW, Iwamoto K, Watanabe M, Kuwahara A, Kaunitz JD. Free fatty acid receptor 3 activation suppresses neurogenic motility in rat proximal colon. Neurogastroenterol Motil. 2018 Jan;30(1).
  4. Iwasaki M, Akiba Y, Kaunitz JD. Duodenal chemosensing. Curr Opin Gastroenterol. 2018 Aug 18.
  5. Kaji I, Kaunitz JD. Luminal chemosensing in the gastroduodenal mucosa. Curr Opin Gastroenterol. 2017 Nov;33(6):439-445
  6. Said H, Akiba Y, Narimatsu K, Maruta K, Kuri A, Iwamoto KI, Kuwahara A, Kaunitz JD. FFA3 Activation Stimulates Duodenal Bicarbonate Secretion and Prevents NSAID-Induced Enteropathy via the GLP-2 Pathway in Rats. Dig Dis Sci. 2017 Aug;62(8):1944-1952.
  7. Kaji I, Akiba Y, Furuyama T, Adelson DW, Iwamoto K, Watanabe M, Kuwahara A, Kaunitz JD. Free fatty acid receptor 3 activation suppresses neurogenic motility in rat proximal colon. Neurogastroenterol Motil. 2017 Jul
  8. Akiba Y, Maruta K, Narimatsu K, Said H, Kaji I, Kuri A, Iwamoto KI, Kuwahara A, Kaunitz JD. FFA2 activation combined with ulcerogenic COX inhibition induces duodenal mucosal injury via the 5-HT pathway in rats. Am J Physiol Gastrointest Liver Physiol. 2017 May
  9. Kaji I, Akiba Y, Kato I, Maruta K, Kuwahara A, Kaunitz JD. Xenin Augments Duodenal Anion Secretion via Activation of Afferent Neural Pathways. J Pharmacol Exp Ther. 2017 361:151-161.
  10. Berg CJ, Kaunitz JD. Gut chemosensing: implications for disease pathogenesis. F1000Res. 2016 30;5:2424.
  11. Said H, Kaunitz JD. Gastrointestinal defense mechanisms. Curr Opin Gastroenterol. 2016 Nov;32(6):461-466.
  12. Kaji I, Akiba Y, Konno K, Watanabe M, Kimura S, Iwanaga T, Kuri A, Iwamoto K, Kuwahara A, Kaunitz JD. Neural FFA3 activation inversely regulates anion secretion evoked by nicotinic ACh receptor activation in rat proximal colon. J Physiol. 2016 15;594:3339-52.
  13. Kaji I, Akiba Y, Said H, Narimatsu K, Kaunitz JD. Luminal 5-HT stimulates colonic bicarbonate secretion in rats. Br J Pharmacol. 2015 172:4655-70.
  14. Akiba Y, Kaunitz JD, Higuchi K. The effects of a TGR5 agonist and a dipeptidyl peptidase IV inhibitor on dextran sulfate sodium-induced colitis in mice. J Gastroenterol Hepatol. 2015 30 Suppl 1:60-5.
  15. Fujiwara K, Inoue T, Yorifuji N, Iguchi M, Sakanaka T, Narabayashi K, Kakimoto K, Nouda S, Okada T, Ishida K, Abe Y, Masuda D, Takeuchi T, Fukunishi S, Umegaki E, Akiba Y, Kaunitz JD, Higuchi K. Combined treatment with dipeptidyl peptidase 4 (DPP4) inhibitor sitagliptin and elemental diets reduced indomethacin-induced intestinal injury in rats via the increase of mucosal glucagon-like peptide-2 concentration. J Clin Biochem Nutr. 2015 56:155-62.

About Dr. Kauntiz

Dr. Kaunitz is a professor of medicine at UCLA Vatche & Tamar Manoukian Division of Digestive Diseases, and senior clinical-scientist investigator at VA Greater Los Angeles Health Care. He studies mucosal defense and transport pathways of the upper gastrointestinal tract. Collaborating with Dr. Yasutada Akiba, he has studied the uptake mechanism of the potent bacterial toxin lipopolysaccharide (LPS) from the intestinal lumen into the enterocyte. LPS is a key driver of the increased inflammatory tone characteristic of metabolic syndrome. He is currently testing the novel hypothesis that LPS enters the circulation by distinct trans-epithelial endocytic mechanisms that require luminal lipid, with "healthy fats" such as n-3 polyunsaturated fatty acids and "unhealthy" fats such as saturated long-chain fatty acids promoting LPS uptake by different pathways, perhaps explaining their differential effects on inflammation. Further studies have shown that these endocytic mechanisms are activated by luminal signals, providing potential targets for drugs aimed at limiting LPS uptake and decreasing the concentration of LPS in the blood, therefore decreasing the systemic inflammation that is a likely cause the metabolic syndrome.

Dr. Kaunitz's lab also produced the gut selective dual oxidase (DUOX) knockout mouse model that, in collaboration with other labs, has been used to demonstrate that DUOX, through its generation of peroxide and other reactive oxygen species (ROS), affects the composition of the gut microbiome that may alter susceptibility to IBD. DUOX may also decrease the infectivity of enveloped viruses such as influenza and COVID-19. Dr. Kaunitz has proposed and shown data that dietary supplementation with iodine or SCN may serve as an inexpensive means of decreasing viral infections in large populations.