Gut microbiota compositional and functional fingerprint in patients with alcohol use disorder and alcohol‐associated liver disease

Abstract

Background & aims Alcohol use disorder (AUD) represents the most common cause of liver disease. The gut microbiota plays a critical role in the progression of alcohol‐related liver damage. Aim of this study was to characterize the gut microbial composition and function in AUD patients with alcohol‐associated liver disease (AALD). Methods This study included 36 AUD patients (14 with cirrhosis) who were active drinkers and an equal number of matched controls. Stool microbial composition, serum levels of lipopolysaccharide, cytokines/chemokines and gut microbiota functional profile were assessed. Results AUD patients had a decreased microbial alpha diversity as compared to controls (0.092 vs 0.130, P = .047) and a specific gut microbial signature. The reduction of Akkermansia and the increase in Bacteroides were able to identify AUD patients with an accuracy of 93.4%. Serum levels of lipopolysaccharide (4.91 vs 2.43, P = .009) and pro‐inflammatory mediators (tumour necrosis factor alpha 60.85 vs 15.08, P = .001; interleukin [IL] 1beta 4.43 vs 1.72, P = .0001; monocyte chemoattractant protein 1 225.22 vs 16.43, P = .006; IL6 1.87 vs 1.23, P = .008) were significantly increased in AUD patients compared to controls and in cirrhotic patients compared to non‐cirrhotic ones (IL6 3.74 vs 1.39, P = .019; IL8 57.60 vs 6.53, P = .004). The AUD‐associated gut microbiota showed an increased expression of gamma‐aminobutyric acid (GABA) metabolic pathways and energy metabolism. Conclusions AUD patients present a specific gut microbial fingerprint, associated with increased endotoxaemia, systemic inflammatory status and functional alterations that may be involved in the progression of the AALD and in the pathogenesis of AUD.

Changes in the fecal bacterial microbiota associated with disease severity in alcoholic hepatitis patients

“…27 Recently, Addolorato et al published their findings of significant Akkermansia reduction in patients with alcohol use disorder, irrespective of the degree of liver disease. 28 In line, Grander et al found a depletion of Akkermansia in fecal samples from alcoholic hepatitis patients and Akkermansia supplementation protected mice against liver injury in experimental alcoholic liver disease. 29 Our study suggests that the reduction in Akkermansia abundance is related to the degree of liver inflammation as seen on liver biopsy in patients with alcoholic hepatitis.…”

Circulating Mitochondrial-Derived Vesicles, Inflammatory Biomarkers and Amino Acids in Older Adults With Physical Frailty and Sarcopenia: A Preliminary BIOSPHERE Multi-Marker Study Using Sequential and Orthogonalized Covariance Selection – Linear Discriminant Analysis

“…The panel was designed based on previous studies in older adults and their involvement in pathways and processes relevant to PF&S pathophysiology (i.e., inflammation, amino acid metabolism, and mitochondrial dysfunction) (Calvani et al, 2018b(Calvani et al, , 2020aMarzetti et al, 2019;Picca et al, 2019aPicca et al, , 2020b. Twenty-seven inflammatory mediators including cytokines, chemokines, and growth factors were assayed using the Bio-Plex Pro TM Human Cytokine 27-plex Assay kit (#M500KCAF0Y, Bio-Rad Laboratories Inc., Hercules, CA, USA) on a Bio-Plex R System with Luminex xMAP R Technology (Bio-Rad Laboratories), as described elsewhere (Ponziani et al, 2018(Ponziani et al, , 2019Marzetti et al, 2019;Picca et al, 2019a;Addolorato et al, 2020). Serum levels of C-reactive protein (CRP), myeloperoxidase (MPO), fibroblast growth factor (FGF) 21, and brain-derived neurotrophic factor (BDNF) were measured by using commercially available kits on an ELLA TM automated immunoassay system (Bio-Techne, San Jose, CA, USA).…”

Intestinal permeability, microbial translocation, changes in duodenal and fecal microbiota, and their associations with alcoholic liver disease progression in humans

“…18 Human studies generally focused on the role of the gutliver axis in severe alcoholic hepatitis and decompensated cirrhosis. [19][20][21][22][23] Little is known about the mechanisms operating at earlier stages of ALD and only two studies reported increased intestinal permeability (IP) in association with alterations of the fecal microbiota in less than 50% of AUD patients. 24,25 Liver disease was not assessed in these reports.…”