Increasing Expiratory Hydrogen in Lactose Intolerance Is Associated with Additional Food Intolerance/Malabsorption

Single and/or combined food intolerance/malabsorption may cause nonspecific, functional gastrointestinal (GI) complaints. In lactose-intolerant patients we evaluated the influence of additional food intolerance/malabsorption with hydrogen (H2) breath tests. In a retrospective analysis of charts from 279 lactose-intolerant patients, we found 128 patients with only lactose intolerance (LIT). Then, we identified 106 LIT patients with additional histamine intolerance (HIT). Additionally, 45 LIT and HIT patients also had fructose malabsorption (FM). A hydrogen (H2) breath test was performed to evaluate LIT and FM. A serum diamine oxidase value of <10 U/mL and a response to a histamine-reduced diet was used to identify HIT. Using pairwise comparison with the Kruskal–Wallis test to associate the area under the curve (AUC) of LIT patients and, LIT with HIT, to LIT with HIT and FM it was found, that the exhaled hydrogen values were significantly higher in patients with two-fold and triple combined food intolerance/malabsorption (p < 0.004 and p < 0.001, respectively). Within the pool of 170 LIT patients with >20 ppm increase of expiratory H2 from baseline, there were 74 LIT-only patients, 60 LIT with HIT patients, and 36 LIT patients with additional HIT and FM. With the Kruskal–Wallis test AUCs demonstrated a significant difference between all three groups (p = 0.024). In patients with LIT, the presence of additional food intolerance/malabsorption, significantly increases expiratory H2 values. We demonstrate evidence, which may suggest HIT to embody an own GI disorder as food intolerance/malabsorption

Serum Diamine Oxidase Values, Indicating Histamine Intolerance, Influence Lactose Tolerance Breath Test Results

Lactose intolerance (LIT) is one of the major causes of irritable bowel syndrome (IBS) spectrum complaints. Differences in inadequate lactose digestion are described as various LIT phenotypes with basically unknown pathophysiology. In LIT patients, we retrospectively assessed the effect of histamine intolerance (HIT) on expiratory hydrogen (H2) during H2 lactose breath tests. In a retrospective evaluation of charts from 402 LIT patients, 200 patients were identified as having only LIT. The other 202 LIT patients were found to additionally have diamine oxidase (DAO) values of <10 U/mL, which indicates histamine intolerance (HIT). To identify HIT, standardized questionnaires, low serum DAO values and responses to a histamine-reduced diet were used. Patients were separated into three diagnostic groups according to the result of H2 breath tests: (1) LIT, with an H2 increase of >20 parts per million (ppm), but a blood glucose (BG) increase of >20 mg/dL, (2) LIT with an H2 increase of 20 ppm in combination with a BG increase of <20 mg/dL, and (3) LIT with an exhaled H2 increase of <20 ppm and BG increase of <20 mg/dL. Pairwise comparison with the Kruskal Wallis test was used to compare the areas under the curve (AUC) of LIT and LIT with HIT patients. Exhaled H2 values were significantly higher in H2 > 20 ppm and BG < 20 mg/dL patients with LIT and HIT (p = 0.007). This diagnostic group also showed a significant higher number of patients (p = 0.012) and a significant higher number of patients with gastrointestinal (GI) symptoms during H2 breath tests (p < 0.001). Therefore, low serum DAO values, indicating HIT, influence results of lactose tolerance breath tests

Interindividual differences in aronia juice tolerability linked to gut microbiome and metabolome changes—secondary analysis of a randomized placebo-controlled parallel intervention trial

Abstract Background Aronia melanocarpa is a berry rich in polyphenols known for health benefits. However, the bioavailability of polyphenols has been questioned, and the individual taste acceptance of the fruit with its specific flavor varies. We recently observed substantial differences in the tolerability of aronia juice among healthy females, with half of the individuals tolerating aronia juice without complaints. Given the importance of the gut microbiome in food digestion, we investigated in this secondary analysis of the randomized placebo-controlled parallel intervention study (ClinicalTrials.gov registration: NCT05432362) if aronia juice tolerability was associated with changes in intestinal microbiota and bacterial metabolites, seeking for potential mechanistic insights into the impact on aronia polyphenol tolerance and metabolic outcomes. Results Forty females were enrolled for this 6-week trial, receiving either 100 ml natural aronia juice (verum, V) twice daily or a polyphenol-free placebo (P) with a similar nutritional profile, followed by a 6-week washout. Within V, individuals were categorized into those who tolerated the juice well (Vt) or reported complaints (Vc). The gut microbiome diversity, as analyzed by 16S rRNA gene-based next-generation sequencing, remained unaltered in Vc but changed significantly in Vt. A MICOM-based flux balance analysis revealed pronounced differences in the 40 most predictive metabolites post-intervention. In Vc carbon-dioxide, ammonium and nine O-glycans were predicted due to a shift in microbial composition, while in Vt six bile acids were the most likely microbiota-derived metabolites. NMR metabolomics of plasma confirmed increased lipoprotein subclasses (LDL, VLDL) post-intervention, reverting after wash out. Stool samples maintained a stable metabolic profile. Conclusion In linking aronia polyphenol tolerance to gut microbiota-derived metabolites, our study explores adaptive processes affecting lipoprotein profiles during high polyphenol ingestion in Vt and examines effects on mucosal gut health in response to intolerance to high polyphenol intake in Vc. Our results underpin the importance of individualized hormetic dosing for beneficial polyphenol effects, demonstrate dynamic gut microbiome responses to aronia juice, and emphasize personalized responses in polyphenol interventions. Graphical Abstract Video Abstrac

Obesity Affects HDL Metabolism, Composition and Subclass Distribution

Background: Obesity increases the risk of coronary heart disease, partly due to its strong association with atherogenic dyslipidemia, characterized by high triglycerides and low high-density lipoprotein (HDL) cholesterol levels. Functional impairment of HDL may contribute to the increased cardiovascular mortality, but the effect of obesity on composition, structure, and function of HDL is not well understood. Design and Methods: We determined HDL composition, HDL subclass distribution, parameters of HDL function, and activities of most important enzymes involved in lipoprotein remodeling, including lecithin–cholesterol acyltransferase (LCAT) and cholesteryl ester transfer protein (CETP) in relatively young normal weight (n = 26), overweight (n = 22), and obese (n = 20) women. Results: Obesity (body mass index (BMI) ≥ 30) was associated with noticeable changes in LCAT and CETP activities and altered HDL composition, such as decreased apolipoprotein A-I, cholesterol, and phospholipid content, while pro-inflammatory HDL serum amyloid a content was increased. We observed a marked shift towards smaller HDL subclasses in obesity linked to lower anti-oxidative capacity of serum. LCAT activity, HDL subclass distribution, and HDL-cholesterol were associated with soluble leptin receptor, adiponectin, and liver enzyme activities. Of note, most of these alterations were only seen in obese women but not in overweight women. Conclusions: Obesity markedly affects HDL metabolism, composition, and subclass distribution linked to changes in liver and adipose tissue. HDL dysfunction may contribute to increased cardiovascular risk in obesity