Aims: Chemotherapy can affect the lining of the gut and the digestion of nutrients and consequently cause muscle wasting and physical impairment. This study investigates gut function, by a battery of tests, in advanced cancer patients undergoing chemotherapy.
Methods: In 16 patients with advanced cancer undergoing chemotherapy (T) and 16 healthy controls (H), we performed gut permeability tests using the inert sugars rhamnose (R), lactulose (L), and 3-O-Methyl-D-glucose (3-OMG) to measure L/R and 3-OMG/R ratios. Mucosal function was assessed by pulse IV administration of L-[5-13C-5,5-2H2]-CIT to calculate citrulline (CIT) concentration and production rate. Protein digestion capacity and splanchnic extraction of phenyalanine (PHE) were measured after combined intake of a high-protein meal with enteral [1-13C]PHE and 15N-spirulina, and primed continuous infusion of [ring-2H5]PHE. Blood/urine samples were obtained for inert sugars and amino concentrations/enrichments by LC-MS/MS, and statistical analysis by unpaired t-tests and Spearman correlation tests.
Results: Both T and H groups included 7 females (43.8%) and mean age was comparable (T: 60.1±16.6y, H: 59.3±16.0y, ns). L/R ratio and 3-OMG/R ratios were not different, but 3-OMG was higher in T (T: 48.4±19.7% vs. H: 35.5±13.5%, p=0.03). Protein digestion capacity tended to be lower in T (0.66±0.08 vs. 0.75±0.15, p=0.07), splanchnic extraction was comparable (T: 0.20±0.1 vs. H: 0.21±0.1, ns). Plasma CIT (T: 20.5±8.4 umol/L vs. H: 29.9±9.6 umol/L, p=0.009) and the production of CIT (T: 16.9±7.7 umol/kg FFM*h vs. H: 11.0±3.4 umol/kg FFM*h, p=0.02) were lower in T.
Conclusions: Patients with cancer undergoing chemotherapy show early signs of a leaky gut and impaired digestion and mucosal function.