RESUMO
Objective: Alterations of gut microbiota composition or function may participate in the pathophysiology of several diseases. We aimed to explore the effect of chronic alcohol overconsumption on gut microbial metabolism, as assessed by evaluating 13C-D-xylose breath test results. Materials and methods: We investigated all 13C-D-xylose breath tests performed at Lovisenberg Diaconal Hospital during the years 2005 to 2011, using patient files for diagnosing the patients into one of three patient categories: alcohol overconsumption, coeliac disease and functional bowel disorder. In addition, a group of healthy controls was included. The time curves of 13CO2 excretion in breath samples were divided into two phases, evaluating small intestinal absorption (0-60 min) and colonic microbial metabolism (90-240 min), respectively. Results: A total of 719 patients underwent 13C-D-xylose breath testing during the inclusion period. Thirty-five had a history of alcohol overconsumption, 66 had coeliac disease, and 216 had a functional bowel disorder, while 44 healthy controls were included for comparison. The alcohol overconsumption group had similar small intestinal phase results as the group of patients with untreated coeliac disease. During the colonic phase, the group of patients with alcohol overconsumption differed from all the other groups in terms of 13C-xylose recovery, with significantly less 13CO2 excretion compared to the other groups. Conclusion: The results suggest that patients with a history of alcohol overconsumption suffer from both small intestinal malabsorption and impaired colonic microbial metabolism. The role of gut microbiota in chronic alcohol overconsumption should be investigated further.
RESUMO
BACKGROUND: Alcohol-related morbidity may involve changes in the gut microbiota and immune dysregulation. We have previously demonstrated alterations in gut microbiota composition and functions in patients with alcohol overconsumption, and now aimed to investigate possible associations between cytokine levels, gut microbiota, and clinical symptoms. METHODS: We included hospital inpatients with a history of chronic alcohol overconsumption. For comparison, we included control patients with a low alcohol intake. Cytokine levels (TGF-ß1, TNF-α, IL-10, IL-8, IL-6, IFN-γ, MCP-1, IL-1RA, IL-1ß, and IL-17) were determined using a customized V-plex assay. We then examined associations of cytokine levels with the abundance of Proteobacteria and Faecalibacterium, percentage of the short-chain fatty acid butyrate, psychiatric symptoms (Hospital Anxiety and Depression Scale), and biochemical liver variables. RESULTS: We included 28 patients with alcohol overconsumption (79% men), and 25 control patients (72% men). Patients with alcohol overconsumption had higher levels of IL-6 (p = 0.002), IFN-γ (p = 0.018), and MCP-1 (p = 0.006), and lower levels of TGF-ß1 (p = 0.017) compared with control patients. Inverse correlations were found between Proteobacteria abundance and TNF-α (Rs = -0.55, p = 0.02) and IL-8 (Rs = -0.58, p = 0.014), and between Faecalibacterium and MCP-1 levels (Rs = -0.56, p = 0.02) in the control patients, but not in patients with alcohol overconsumption. Patients with alcohol overconsumption reported more psychiatric symptoms, and these symptoms were inversely correlated with IL-10 levels. There were positive correlations between several of the assessed cytokines and biochemical liver variables, and negative correlations between cytokine levels and albumin. CONCLUSION: Patients with alcohol overconsumption had a cytokine profile suggestive of increased systemic inflammatory activity, with higher levels of pro-inflammatory cytokines (IL-6, IFN-γ, and MCP-1) and lower levels of anti-inflammatory cytokines (TGF-ß1). The findings may represent a link between alcohol use and alcohol-related morbidity.
Assuntos
Alcoolismo/sangue , Biomarcadores/sangue , Citocinas/sangue , Microbioma Gastrointestinal/efeitos dos fármacos , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Feminino , Humanos , Interleucina-1beta/sangue , Masculino , Pessoa de Meia-Idade , Fator de Necrose Tumoral alfa/sangueRESUMO
Excessive alcohol intake can alter the gut microbiota, which may underlie the pathophysiology of alcohol-related diseases. We examined gut microbiota composition and functions in patients with alcohol overconsumption for >10 years, compared to a control group of patients with a history of no or low alcohol intake. Faecal microbiota composition was assessed by 16S rRNA sequencing. Gut microbiota functions were evaluated by quantification of short-chain fatty acids (SCFAs) and predictive metagenome profiling (PICRUSt). Twenty-four patients, mean age 64.8 years (19 males), with alcohol overconsumption, and 18 control patients, mean age 58.2 years (14 males) were included. The two groups were comparable regarding basic clinical variables. Nutritional assessment revealed lower total score on the screening tool Mini Nutritional Assessment, lower muscle mass as assessed by handgrip strength, and lower plasma vitamin C levels in the alcohol overconsumption group. Bacteria from phylum Proteobacteria were found in higher relative abundance, while bacteria from genus Faecalibacterium were found in lower relative abundance in the group of alcohol overconsumers. The group also had higher levels of the genera Sutterella, Holdemania and Clostridium, and lower concentration and percentage of butyric acid. When applying PICRUSt to predict the metagenomic composition, we found that genes related to invasion of epithelial cells were more common in the group of alcohol overconsumers. We conclude that gut microbiota composition and functions in patients with alcohol overconsumption differ from patients with low consumption of alcohol, and seem to be skewed into a putative pro-inflammatory direction.