DepressionFecal calprotectinGut-brain axiskynurenine pathwayLactulose hydrogen breath test

Altered Tryptophan Metabolism on the Kynurenine Pathway in Depressive Patients with Small Intestinal Bacterial Overgrowth

  • 2022
  • Cezary Chojnacki, Paulina Konrad, Aleksandra Błońska, et al.
Why this matters for your gut health

The causes of depression are not fully understood, and nutritional and inflammatory factors are increasingly implicated. Most tryptophan is metabolized in the digestive system, but earlier depression research rarely checked for gut disease. This study links small intestinal bacterial overgrowth (SIBO) to a shift in tryptophan metabolism toward the neurotoxic branch of the kynurenine pathway. It also shows that treating SIBO with rifaximin improved both gut symptoms and depressive symptoms. That suggests gut bacteria may contribute to some mood disorders.

Summary

The study compared 40 healthy controls with 40 patients who had diarrhea-predominant SIBO (confirmed by lactulose hydrogen breath test) and mild to moderate depression. Urinary tryptophan (TRP), kynurenine (KYN), kynurenic acid (KYNA) and quinolinic acid (QA) were measured by LC-MS/MS before and after three months of cyclic rifaximin. Patients with SIBO had higher neurotoxic metabolites (KYN, QA), lower neuroprotective KYNA, and a higher KYN/TRP ratio (suggesting increased IDO enzyme activity). Depression scores correlated with fecal calprotectin, intraepithelial lymphocytes, KYN and QA. Rifaximin improved metabolite ratios, abdominal symptoms and depression scores. The authors conclude that SIBO alters tryptophan metabolism on the kynurenine pathway and may cause both abdominal and mood symptoms. They call for more research, including comparing depressed patients with and without overgrowth.

Key findings

  • KYN was higher in SIBO patients than in controls (0.61 vs 0.41 mg/gCr, p < 0.05), as was QA (4.22 vs 3.15 mg/gCr, p < 0.001). KYNA was lower (2.10 vs 2.44 mg/gCr, p < 0.001).
  • KYN/TRP was higher in SIBO, while KYN/KYNA and KYNA/QA were lower (all p < 0.001), so the balance shifted toward neurotoxic metabolites.
  • CRP (6.72 vs 1.59 mg/L) and fecal calprotectin (46.2 vs 24.5 µg/g) were higher in SIBO patients (both p < 0.05), and HAM-D depression scores were much higher (26.3 vs 9.85, p < 0.001).
  • HAM-D scores correlated positively with QA (rho 0.506, p = 0.0043), intraepithelial lymphocytes (rho 0.375, p = 0.0175), KYN (rho 0.353, p = 0.025) and fecal calprotectin (rho 0.335, p = 0.035). The correlation with CRP was not significant.
  • Rifaximin (1200 mg/day for 14 days, then 10 days a month for two more months) lowered KYN (p < 0.05) and QA (p < 0.001), while the KYNA change was not significant.
  • After rifaximin, KYN/TRP fell (0.048 to 0.04, p < 0.05) and KYNA/QA rose (0.53 to 0.57, p < 0.01).
  • GSRS-IBS abdominal symptom scores fell from 37.5 to 20.6 (p < 0.001), and depression scores fell from 15.5 to 10.2 (p < 0.001).
  • Diarrhea resolved in 82.5% of patients, abdominal pain in 80%, bloating in 67.5% and flatulence in 65%.
  • Mood symptoms, especially anxiety, persisted in 20% of patients, and 15% had transient increases in bloating and flatulence. Rifaximin was otherwise well tolerated.
  • The study had no placebo group, and the paper states that pro-inflammatory cytokines were not measured.
  • The PDF has some internal inconsistencies. Table 1 gives a baseline HAM-D of 26.3, but the text gives 15.5 before treatment. Table 1 also labels the patient group “irritable bowel syndrome (SIBO)”. Check these against the original paper before citing exact figures.

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Citation

Chojnacki C, Konrad P, Błońska A, Medrek-Socha M, Przybylowska-Sygut K, Chojnacki J, Poplawski T. Altered Tryptophan Metabolism on the Kynurenine Pathway in Depressive Patients with Small Intestinal Bacterial Overgrowth. Nutrients. 2022;14(15):3217. doi:10.3390/nu14153217

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