1.
Increased kynurenine-to-tryptophan ratio in the serum of patients infected with SARS-CoV2: An observational cohort study.
Lionetto, L, Ulivieri, M, Capi, M, De Bernardini, D, Fazio, F, Petrucca, A, Pomes, LM, De Luca, O, Gentile, G, Casolla, B, et al
Biochimica et biophysica acta. Molecular basis of disease. 2021;1867(3):166042
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Plain language summary
Covid-19 infection may alter the immune system, but exactly how is still unclear. A key pathway in the regulation of the immune system is the kynurenine pathway of tryptopham. This observational cohort study aimed to determine how this pathway was affected following infection with Covid-19. The results showed that compared to healthy patients, individuals who tested positive to Covid-19 had an increased ratio of kynurenine:tryptopham and the increase was more pronounced in those who had severe infection and if they were male. It was concluded that the kynurenin:tryptopham ratio could be used as a marker for disease severity and useful for treatments. This study could be used by healthcare professionals to use the kynurenine:tryptopham ratio as a marker for disease severity and stratify patients accordingly for treatments.
Abstract
Immune dysregulation is a hallmark of patients infected by SARS-CoV2 and the balance between immune reactivity and tolerance is a key determinant of all stages of infection, including the excessive inflammatory state causing the acute respiratory distress syndrome. The kynurenine pathway (KP) of tryptophan (Trp) metabolism is activated by pro-inflammatory cytokines and drives mechanisms of immune tolerance. We examined the state of activation of the KP by measuring the Kyn:Trp ratio in the serum of healthy subjects (n = 239), and SARS-CoV2-negative (n = 305) and -positive patients (n = 89). Patients were recruited at the Emergency Room of St. Andrea Hospital (Rome, Italy). Kyn and Trp serum levels were assessed by HPLC/MS-MS. Compared to healthy controls, both SARS-CoV2-negative and -positive patients showed an increase in the Kyn:Trp ratio. The increase was larger in SARS-CoV2-positive patients, with a significant difference between SARS-CoV2-positive and -negative patients. In addition, the increase was more prominent in males, and positively correlated with age and severity of SARS-CoV2 infection, categorized as follows: 1 = no need for intensive care unit (ICU); 2 ≤ 3 weeks spent in ICU; 3 ≥ 3 weeks spent in ICU; and 4 = death. The highest Kyn:Trp values were found in SARS-CoV2-positive patients with severe lymphopenia. These findings suggest that the Kyn:Trp ratio reflects the level of inflammation associated with SARS-CoV2 infection, and, therefore, might represent a valuable biomarker for therapeutic intervention.
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Brain fogginess, gas and bloating: a link between SIBO, probiotics and metabolic acidosis.
Rao, SSC, Rehman, A, Yu, S, Andino, NM
Clinical and translational gastroenterology. 2018;9(6):162
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Plain language summary
D-lactic acid is produced by intestinal bacteria and a rise in levels can lead to D-lactic acidosis, causing neurological changes such as slurred speech and gait disturbances. This is frequently observed in short bowel syndrome. This small, observational study aimed to determine if brain fogginess (mental confusion, impaired judgement, poor short-term memory and difficulty concentrating) and intestinal gas and bloating is associated with D-lactic acidosis and small intestinal bacterial overgrowth (SIBO). 38 patients presenting with gas and bloating in the absence of short bowel syndrome, and with or without brain fog were assessed. All patients with brain fog were consuming probiotics, with a higher proportion of them diagnosed with SIBO and D-lactic acidosis, when compared to the non-brain fog group. The researchers stopped probiotics in all patients and administered antibiotics, observing a significant reduction in brain fog and gastrointestinal symptoms. Whilst this is a small, observational study, nutrition practitioners may wish to assess the likelihood of SIBO and D-lactic acidosis before recommending probiotics, especially in the presence of brain fog.
Abstract
BACKGROUND D-lactic acidosis is characterized by brain fogginess (BF) and elevated D-lactate and occurs in short bowel syndrome. Whether it occurs in patients with an intact gut and unexplained gas and bloating is unknown. We aimed to determine if BF, gas and bloating is associated with D-lactic acidosis and small intestinal bacterial overgrowth (SIBO). METHODS Patients with gas, bloating, BF, intact gut, and negative endoscopic and radiological tests, and those without BF were evaluated. SIBO was assessed with glucose breath test (GBT) and duodenal aspiration/culture. Metabolic assessments included urinary D-lactic acid and blood L-lactic acid, and ammonia levels. Bowel symptoms, and gastrointestinal transit were assessed. RESULTS Thirty patients with BF and 8 without BF were evaluated. Abdominal bloating, pain, distension and gas were the most severe symptoms and their prevalence was similar between groups. In BF group, all consumed probiotics. SIBO was more prevalent in BF than non-BF group (68 vs. 28%, p = 0.05). D-lactic acidosis was more prevalent in BF compared to non-BF group (77 vs. 25%, p = 0.006). BF was reproduced in 20/30 (66%) patients. Gastrointestinal transit was slow in 10/30 (33%) patients with BF and 2/8 (25%) without. Other metabolic tests were unremarkable. After discontinuation of probiotics and a course of antibiotics, BF resolved and gastrointestinal symptoms improved significantly (p = 0.005) in 23/30 (77%). CONCLUSIONS We describe a syndrome of BF, gas and bloating, possibly related to probiotic use, SIBO, and D-lactic acidosis in a cohort without short bowel. Patients with BF exhibited higher prevalence of SIBO and D-lactic acidosis. Symptoms improved with antibiotics and stopping probiotics. Clinicians should recognize and treat this condition.