## 1 Introduction  
The metabolism of Tryptophan (Trypt) through the Kynureine pathway (KP) is complex and is involved in immunological and inflammatory disorders, psychiatric illness, cognition, pain, metabolic and endocrine diseases, exercise, and others [1; 2; 3; 4]. These disorders often occur together and have shared biological characteristics, such as low-grade chronic inflammation and dysregulation of the KP [4; 5; 6; 7; 8; 9; 10; 11].  
Monitoring the KP has not been standardised. Both concentrations of the metabolites and ratios between the concentrations have been reported [12]. The ratios measure the enzyme activity and sometimes reflect the metabolites' functions more precisely than the concentrations.  
Figure 1 shows an overview of the Trypt-Kynureine (Kyn) metabolism with the metabolites and the five enzymes of relevance for this paper [10]:  
* Tryptophan 2,3-dioxygenase (TDO) and indoleamine 2,3 dioxygenase (IDO) regulate the Trypt to Kyn step.
* Kynureine aminotransferase (KAT) regulate the steps from Kyn to Kynureine acid (KA) and 3 OH-Kyn to Xanthurenic acid (XA).  
Vitamin B6 (pyridoxal 5-phosphate) is an essential cofactor for KAT, KMO, and KYNU. The enzymatic activity is continuously influenced by hormones, oxidative and antioxidative processes, inflammation, and other biosystems [10,12].  
The effects of the KP metabolites and ratios are only partly understood. Inflammation shunts the Trypt metabolism from serotonin towards Kyn and increases the Kyn/Trypt ratio [1]. Muscular exercise shifts the Kyn metabolism towards the production of KA and increases the KA/Kyn ratio [3]. KA is neuroprotective and anti-inflammatory; QA is a proinflammatory neurotoxic mediator in the brain; and the KA/QA ratio has been considered neuroprotective [1,13,14]. KA and XA are structurally related and involved in the dopamine regulation in the brain. An imbalance in the KA/XA ratio may result in mood disorders [15]. Elevated levels of KA and XA have been reported in subjects with diabetes mellitus (DM), and both have been ascribed diabetogenic effects by inhibiting proinsulin and insulin synthesis [2,8]. QA reduces serum glucose, and the QA/XA ratio has been positively associated with good insulin sensitivity and glucose control [2,8].  
The KP has been thoroughly studied in subjects with psychiatric illness, such as anxiety, depression, suicide, psychosis, schizophrenia, and cognitive deficits. [1,3,4,16,17]. The importance of the KP for less severe, everyday psychosomatic complaints is scarcely evaluated. Some studies have shown disturbed KP in subjects with chronic fatigue syndrome and fibromyalgia [11,18]. Subjects with morbid obesity have an upregulated KP that normalises after bariatric surgery and a high prevalence of metabolic and psychosomatic comorbidity, making them suitable for research of bio-psycho-social interactions. [7,8,10]. The disturbed KP in subjects with obesity is expected to be associated with common psycho-somatic comorbidities, such as perceived general health, muscle-skeletal pain, well-being, mood disorders, fatigue, self-esteem, sleepiness, and sense of humour. However, to our knowledge, no such studies have been performed.  
Thus, the paramount aim was to study the peripheral KP and psychosomatic comorbidity in subjects with morbid obesity undergoing bariatric surgery. Specific aims: (1) Explore associations between the KP and psychosomatic complaints; (2) Study changes in the KP from six months before to six months after bariatric surgery; (3) Explore predictors of the KP.  
Figure 1: Schematic outline of the Kynurenine pathway limited to the steps presented in this paper. TDO: Tryptophan 2,3-dioxygenase. IDO: indoleamine 2,3 dioxygenase. KAT: Kynurenine aminotransferase. KUNU: Kynureninase. KMO: kynureine 3-monooxygenase. B6: Vitamin B6.