Globally, ∼70% of adults are deficient in intestinal lactase, the enzyme required for the digestion of lactose. In these individuals, the consumption of lactose-containing milk and dairy products can lead to the development of various gastrointestinal (GI) symptoms. The primary solution to lactose intolerance is withdrawing lactose from the diet either by eliminating dairy products altogether or substituting lactose-free alternatives. However, studies have shown that certain individuals erroneously attribute their GI symptoms to lactose and thus prefer to consume lactose-free products. This has raised the question whether consuming lactose-free products reduces an individual's ability to absorb dietary lactose and if lactose-absorbers should thus avoid these products. This review summarizes the current knowledge regarding the acclimatization of lactose processing in humans. Human studies that have attempted to induce intestinal lactase expression with different lactose feeding protocols have consistently shown lack of enzyme induction. Similarly, withdrawing lactose from the diet does not reduce intestinal lactase expression. Evidence from cross-sectional studies shows that milk or dairy consumption is a poor indicator of lactase status, corroborating the results of intervention studies. However, in lactase-deficient individuals, lactose feeding supports the growth of lactose-digesting bacteria in the colon, which enhances colonic lactose processing and possibly results in the reduction of intolerance symptoms. This process is referred to as colonic adaptation. In conclusion, endogenous lactase expression does not depend on the presence of dietary lactose, but in susceptible individuals, dietary lactose might improve intolerance symptoms via colonic adaptation. For these individuals, lactose withdrawal results in the loss of colonic adaptation, which might lower the threshold for intolerance symptoms if lactose is reintroduced into the diet.

PurposeAthletes frequently experience gastrointestinal (GI) symptoms during training and competition. Although the prevalence of exercise-induced GI symptoms is high, the mechanisms leading to GI distress during exercise are not fully understood. The aim of this study was to identify running-induced changes in intestinal permeability and markers of GI function and investigate their association with gastrointestinal symptoms.MethodsWe recruited 17 active runners who we allocated as either asymptomatic or symptomatic based on their history of experiencing GI symptoms during running. The participants took part in a running test where they were asked to run for 90 min at 80% of their best 10 km race speed. Intestinal permeability was measured at baseline and after the running test. Levels of serum intestinal fatty acid-binding protein (I-FABP), zonulin, bacterial lipopolysaccharide (LPS), and fecal calprotectin were also measured at baseline and after the running test.ResultsRunning induced a significant increase in intestinal permeability and serum I-FABP concentration but there were no differences between asymptomatic and symptomatic runners. Serum LPS activity did not change from baseline following the running test but the symptomatic group exhibited higher LPS activity at baseline compared to the asymptomatic runners.ConclusionsRunning for 90 min at a challenging pace causes small intestinal damage and increases intestinal permeability. However, these alterations in GI function do not appear to correlate with the development of GI symptoms during running.

Increased luminal bile acid hydrophobicity is associated with cytotoxicity and has been suggested to contribute to gut barrier dysfunction. The aim of this study was to compare 2 high-fat diets and a low-fat diet as to whether they modify fecal bile acid profile and hydrophobicity and/or susceptibility to dextran sodium sulfate (DSS) colitis in C57Bl/6J mice. Control and DSS-Control groups received a low-fat control diet [5.5% of total energy (E%) soy oil, 4.5 E% lard], and the DSS-Lard (5.5 E% soy oil, 54.5 E% lard) and DSS-Fish oil (5.5 E% soy oil, 27.2 E% lard and 27.2% menhaden oil) groups received high-fat diets. Feces for bile acid analysis were collected after 3-wk feeding, followed by induction of dextran DSS colitis (2 d 5% DSS in drinking water + 2 d tap water). Fecal bile acid hydrophobicity was elevated 76% in the lard group (P = 0.051) and 122% in the fish oil group (P = 0.001) compared with control, indicating potentially increased cytotoxicity. DSS caused severe colitis symptoms, evaluated as rectal bleeding, whereas all the controls were symptom free. The median symptom scores were: DSS-Control, 2.3 (IQR = 0.6, 3.0); DSS-Lard, 0.3 (IQR = 0, 2.3); and DSS-Fish oil, 2.4 (IQR = 1.9, 2.8). The only differences were DSS-Control vs. control (P < 0.001) and DSS-Fish oil vs. control (P < 0.001). Severity of symptoms in all colitic mice was positively correlated with fecal bile acid hydrophobicity (Spearman's ρ = 0.43; P = 0.028) and fecal deoxycholic acid concentration (Spearman's ρ = 0.39; P = 0.048). These results suggest that luminal bile acid modification, induced by altered dietary fat composition, may alter susceptibility to DSS colitis.

PurposeChemotherapy-induced gastrointestinal toxicity (CIGT) is a complex process that involves multiple pathophysiological mechanisms. We have previously shown that commonly used chemotherapeutics 5-fluorouracil, oxaliplatin, and irinotecan damage the intestinal mucosa and increase intestinal permeability to iohexol. We hypothesized that CIGT is associated with alterations in fecal microbiota and metabolome. Our aim was to characterize these changes and examine how they relate to the severity of CIGT.MethodsA total of 48 male Sprague–Dawley rats were injected intraperitoneally either with 5-fluorouracil (150 mg/kg), oxaliplatin (15 mg/kg), or irinotecan (200 mg/kg). Body weight change was measured daily after drug administration and the animals were euthanized after 72 h. Blood, urine, and fecal samples were collected at baseline and at the end of the experiment. The changes in the composition of fecal microbiota were analyzed with 16S rRNA gene sequencing. Metabolic changes in serum and urine metabolome were measured with 1 mm proton nuclear magnetic resonance (1H-NMR).ResultsIrinotecan increased the relative abundance of Fusobacteria and Proteobacteria, while 5-FU and oxaliplatin caused only minor changes in the composition of fecal microbiota. All chemotherapeutics increased the levels of serum fatty acids and N(CH3)3 moieties and decreased the levels of Krebs cycle metabolites and free amino acids.ConclusionsChemotherapeutic drugs, 5-fluorouracil, oxaliplatin, and irinotecan, induce several microbial and metabolic changes which may play a role in the pathophysiology of CIGT. The observed changes in intestinal permeability, fecal microbiota, and metabolome suggest the activation of inflammatory processes.Electronic supplementary materialThe online version of this article (doi:10.1007/s00280-017-3364-z) contains supplementary material, which is available to authorized users.