Gut dysbiosis and body composition in cirrhosis

Table 1 Characteristics of the enrolled patients

Parameter	Value
Age, yr	55 [43-61]
Male/Female	18/28
Etiology:
Alcohol	15 (32.6%)
Hepatitis C virus	5 (10.9%)
Primary biliary cholangitis	4 (8.7%)
Primary sclerosing cholangitis	2 (4.3%)
Autoimmune hepatitis	5 (10.9%)
Metabolic-associated liver disease	4 (8.7%)
Wilson disease	3 (6.5%)
Mixed	3 (6.5%)
Cryptogenic	5 (10.9%)
Red blood cells, 1012/L	4.1 [3.5-4.8]
White blood cells, 109/L	4.9 [3.1-6.3]
Platelets, 109/L	105 [76-150]
Serum albumin, g/L	37 [33-41]
Serum total bilirubin, μmol/L	28 [16-56]
Prothrombin (Quick test), %	70 [60-89]
Ascites: grade 2-3, n (%)	9 (19.6%)
Esophageal varices: grade 2-3, n (%)	17 (36.9%)
Spleen length, cm	15.4 [13.1-17.1]
Portal vein diameter, mm	13.0 [11.0-14.2]
Hepatic encephalopathy, n (%)	15 (32.5%)
Child-Pugh class: A/B/C	14/21/11

Table 2 Comparison of the main characteristics, body composition, and the abundance of major taxa of the gut microbiome between patients with cirrhosis and healthy persons

	Patients with cirrhosis (n = 46)	Healthy persons (n = 14)	P
Age, yr	55 [43-61]	51 [41-63]	0.484
Male/Female	18/28	3/11	0.187
Body mass index, kg/m2	27.0 [23.6-30.1]	21.1 [19.7-26.0]	0.002
Fat mass, %	34.7 [28.1-43.5]	24.5 [20.7-31.2]	0.002
Free-fat mass, %	65.3 [56.5-71.9]	75.5 [68.8-79.3]	0.002
Body cell mass, %	32.4 [28.0-36.5]	44.5 [38.4-46.0]	< 0.001
(Body cell mass)/(free-fat mass)	0.50 [0.46-0.55]	0.58 [0.55-0.60]	< 0.001
Extracellular fluid, %	20.1 [17.4-21.4]	18.6 [16.8-19.3]	0.044
Total fluid, %	47.9 [42.0-53.3]	51.7 [46.8-52.9]	0.238
(Extracellular fluid)/(total fluid)	0.41 [0.40-0.43]	0.36 [0.36-0.37]	< 0.001
Phase angle, °	5.3 [4.9-6.3]	7.0 [6.2-7.3]	< 0.001
Firmicutes	38.6 [27.7-52.9]	90.8 [85.7-94.1]	< 0.001
Bacteroidetes	38.6 [26.6-58.5]	5.9 [4.7-8.1]	< 0.001
Proteobacteria	5.5 [2.3-10.6]	0.4 [0.1-0.5]	< 0.001
Clostridia	36.2 [24.8-50.0]	89.3 [86.7-91.0]	< 0.001
Bacilli	0.4 [0.2-1.1]	0.1 [0.0-0.2]	< 0.001

Table 3 Patients grouped with respect to excess fat mass

	Patients with excess fat mass (n = 23)	Patients without excess fat mass (n = 23)	P
Age, yr	58 [49-62]	45 [39-59]	0.033
Male/Female	3/20	15/8	< 0.001
Body mass index, kg/m2	29.7 [27.0-35.6]	23.6 [22.0-27.1]	< 0.001
Body fat, %	43.5 [37.6-47.3]	28.1 [23.1-31.2]	< 0.001
Free-fat mass, %	56.5 [52.7-62.4]	71.9 [68.8-76.9]	< 0.001
Body cell mass, %	29.6 [25.6-33.9]	34.9 [31.2-40.6]	0.001
(Body cell mass)/(free-fat mass)	0.51 [0.45-0.56]	0.49 [0.46-0.53]	0.231
Extracellular fluid, %	17.6 [16.7-18.8]	21.1 [20.4-22.4]	< 0.001
Total fluid, %	42.0 [38.5-45.8]	52.6 [50.4-56.3]	< 0.001
(Extracellular fluid)/(total fluid)	0.42 [0.41-0.43]	0.40 [0.39.2-0.41]	0.005
Phase angle, °	5.4 [5.2-6.6]	5.1 [4.6-5.8]	0.093
Red blood cells, 1012/L	4.5 [3.9-4.8]	3.9 [3.3-4.6]	0.097
White blood cells, 109/L	5.0 [3.6-6.3]	4.7 [2.9-5.7]	0.465
Platelets, 109/L	104 [77-150]	106 [72-150]	0.945
Serum albumin, g/L	37.6 [34.4-42.9]	34.4 [31.3-38.1]	0.030
Serum total bilirubin, μmol/L	20.1 [13.5-36.9]	46.6 [19.1-77.9]	0.037
Prothrombin (Quick test), %	75 [69-92]	64 [40-80]	0.022
Ascites: grade 2-3	1 (4.3%)	8 (34.8%)	0.011
Esophageal varices: grade 2-3	8 (34.8%)	9 (39.1%)	0.500
Spleen length, cm	15.3 [13.0-17.2]	15.7 [13.1-17.1]	0.759
Portal vein diameter, mm	12.7 [11.0-14.2]	13.0 [11.0-14.4]	0.803
Hepatic encephalopathy	4 (17.4%)	9 (39.1%)	0.095
Child-Pugh score	7 [6-9]	9 [7-12]	0.018
Bacteroidetes	46.1 [33.0-61.0]	35.2 [18.3-44.1]	0.039
Barnesiellaceae	0.92 [0.43-2.04	0.04 [0.00-0.11]	0.016
Marinifilaceae	0.66 [0.21-1.03]	0.17 [0.00-0.49]	0.006
Desulfobacteria	0.55 [0.29-1.53]	0.18 [0.01-0.45]	0.032
Bilophila	0.36 [0.04-1.30]	0.04 [0.00-0.18]	0.016
Coriobacteriaceae	0.09 [0.04-0.56]	0.03 [0.00-0.06]	0.004
Eggerthellaceae	0.08 [0.03-0.20]	0.03 [0.01-0.06]	0.028
Senegalimassilia	0.01 [0.00-0.05]	0.00 [0.00-0.00]	0.040
Slackia	0.01 [0.00-0.05]	0.00 [0.00-0.00]	0.004
Parasutterella	0.01 [0.00-0.19]	0.00 [0.00-0.00]	0.015
Odoribacter	0.10 [0.03-0.24]	0.26 [0.16-0.52]	0.047
Veillonella	0.01 [0.00-0.07]	0.16 [0.01-0.82]	0.012
Clostridiaceae	0.01 [0.00-0.05]	0.07 [0.00-0.29]	0.041

Only significant changes in the gut microbiome are indicated.

Table 4 Significant correlations between the volumes of the body components and the taxa of the gut microbiome

	Fat mass	Body cell mass	Extracellular fluid
Bacteroidetes	r = 0.329; P = 0.026	NS	NS
Desulfobacteria	r = 0.347; P = 0.018	NS	NS
Firmicutes	NS	NS	r = -0.386; P = 0.008
Proteobacteria	NS	NS	r = 0.320; P = 0.031
Bacilli	NS	NS	r = -0.378; P = 0.009
Clostridia	NS	NS	r = -0.305; P = 0.039
Bacteroidaceae	NS	r = -0.294; P = 0.047	NS
Barnesiellaceae	r = 0.291; P = 0.049	r = 0.332; P = 0.024	NS
Clostridiaceae	r = -0.326; P = 0.027	NS	NS
Coriobacteriaceae	r = 0.319; P = 0.031	NS	NS
Erysipelatoclostridiaceae	NS	r = 0.310; P = 0.036	NS
Anaerotruncus	NS	r = 0.338; P = 0.022	NS
Bilophila	r = 0.383; P = 0.009	NS	r = 0.294; P = 0.048
Campylobacter	r = -0.404; P = 0.005	NS	NS
Catenibacterium	NS	r = 0.306; P = 0.040	NS
Collinsella	r = 0.319; P = 0.031	NS	NS
Megamonas	r = 0.337; P = 0.022	NS	NS
Oscillospira	NS	r = 0.375; P = 0.010	NS
Parasutterella	r = 0.365; P = 0.013	NS	NS
Senegalimassilia	ns	r = 0.379; P = 0.009	NS
Slackia	r = 0.439; P = 0.002	NS	NS
Veillonella	r = -0.308; P = 0.037	r = -0.294; P = 0.047	NS

NS: Not significant.

Table 5 Patients grouped with respect to body cell mass deficiency

	Patients with body cell mass deficiency (n = 15)	Patients without body cell mass deficiency (n = 31)	P
Age, yr	56 [46-63]	49 [39-61]	0.331
Male/Female	4/11	14/17	0.190
Body mass index, kg/m2	27.0 [23.8-29.0]	27.1 [23.2-30.9]	0.806
Body fat, %	33.6 [29.8-42.7]	36.3 [27.3-44.9]	0.656
Free-fat mass, %	66.4 [57.3-70.2]	63.7 [55.1-72.7]	0.656
Body cell mass, %	29.0 [25.6-31.9]	34.7 [30.0-37.1]	0.002
(Body cell mass)/(free-fat mass)	0.45 [0.41-0.46]	0.53 [0.49-0.56]	< 0.001
Extracellular fluid, %	20.4 [17.7-21.1]	19.6 [17.0-21.8]	0.648
Total fluid, %	48.6 [42.0-51.5]	47.1 [41.0-53.3]	0.926
(Extracellular fluid)/(total fluid)	0.42 [0.41-0.43]	0.41 [0.39-0.43]	0.223
Phase angle, °	4.5 [4.2-4.6]	5.8 [5.2-6.5]	< 0.001
Red blood cells, 1012/L	3.8 [3.5-4.6]	4.2 [3.6-4.8]	0.211
White blood cells, 109/L	4.1 [3.0-7.2]	5.1 [3.3-5.9]	0.159
Platelets, 109/L	116 [77-170]	101 [72-142]	0.211
Serum albumin, g/L	34.1 [29.3-37.3]	37.6 [33.3-42.4]	0.028
Serum total bilirubin, μmol/L	46.6 [18.7-66.2]	22.3 [15.0--54.6]	0.314
Prothrombin (Quick test), %	71 [54-92]	70 [60-86]	0.981
Ascites: grade 2-3	4 (26.7%)	5 (16.1%)	0.320
Esophageal varices: grade 2-3	4 (26.7%)	13 (41.9%)	0.251
Spleen length, cm	15.8 [13.4-17.0]	15.3 [13.0-17.2]	0.864
Portal vein diameter, mm	13.8 [11.0-14.4]	12.7 [11.0-14.2]	0.695
Hepatic encephalopathy	7 (46.7%)	8 (25.8%)	0.141
Child-Pugh score	9 [7-11]	7 [6-9]	0.092
Bacteroidaceae	22.7 [6.8-40.8]	4.0 [1.4-20.5]	0.041
Eggerthella	0.01 [0.00-0.03]	0.00 [0.00-0.00]	0.001
Erysipelatoclostridiaceae	0.02 [0.01-0.08]	0.11 [0.04-0.25]	0.006
Coprococcus	0.24 [0.06-0.68]	0.68 [0.16-1.26]	0.033
Intestinimonas	0.00 [0.00-0.03]	0.03 [0.01-0.07]	0.028
Desulfovibrio	0.00 [0.00-0.01]	0.02 [0.00-0.38]	0.043
Catenibacterium	0.00 [0.00-0.00]	0.00 [0.00-0.20]	0.021
Senegalimassilia	0.00 [0.00-0.00]	0.00 [0.00-0.03]	0.015

Only significant changes in the gut microbiome are indicated.

Table 6 Patients grouped with respect to excess extracellular fluid

	Patients with excess extracellular fluid (n = 22)	Patients without excess extracellular fluid (n = 24)	P
Age, yr	53 [39-61]	57 [44-62]	0.545
Male/Female	10/12	8/16	0.300
Body mass index, kg/m2	28.1 [24.2-31.2]	26.8 [22.9-29.1]	0.129
Body fat, %	32.4 [24.5-44.9]	36.7 [30.4-42.7]	0.391
Free-fat mass, %	67.6 [55.1-75.5]	63.3 [57.3-69.6]	0.391
Body cell mass, %	33.6 [28.0-40.6]	32.2 [28.2-35.2]	0.545
(Body cell mass)/(free-fat mass)	0.50 [0.45-0.55]	0.49 [0.47-0.55]	0.921
Extracellular fluid, %	20.9 [17.7-22.6]	18.5 [17.2-20.4]	< 0.001
Total fluid, %	50.8 [41.2-55.9]	45.9 [42.0-50.9]	0.169
(Extracellular fluid)/(total fluid)	0.43 [0.40-43.3]	0.41 [0.39-0.42]	0.042
Phase angle, °	5.4 [4.6-6.3]	5.2 [4.9-6.3]	0.879
Red blood cells, 1012/L	4.2 [3.4-4.8]	4.0 [3.6-4.6]	0.991
White blood cells, 109/L	4.6 [2.4-6.3]	5.2 [3.4-6.2]	0.419
Platelets, 109/L	89 [72-113]	124 [76-158]	0.082
Serum albumin, g/L	34.5 [30.4-41.3]	37.5 [34.3-40.7]	0.113
Serum total bilirubin, μmol/L	39.4 [18.5-66.2]	24.8 [15.4-44.5]	0.684
Prothrombin (Quick test), %	61 [40-86]	76 [70-91]	0.012
Ascites: grade 2-3	9 (40.9%)	0	0.001
Esophageal varices: grade 2-3	9 (40.9%)	8 (33.3%)	0.410
Spleen length, cm	16.7 [14.8-18.2]	14.4 [12.4-16.4]	0.021
Portal vein diameter, mm	13.5 [11.0-15.0]	12.5 [11.0-14.0]	0.180
Hepatic encephalopathy	10 (45.5%)	5 (20.8%)	0.050
Child-Pugh score	9 [6-12]	7 [6-9]	0.088
Proteobacteria	8.93 [5.58-22.60]	2.84 [1.61-5.66]	< 0.001
Firmicutes	31.4 [26.6-44.6]	43.6 [33.4-58.7]	0.023
Oscillospiraceae	4.43 [1.57-8.46]	8.33 [5.00-12.9]	0.024
Rikenellaceae	0.98 [0.03-1.78]	2.83 [0.85-5.51]	0.002
Actinobacteria	0.56 [0.11-1.43]	1.21 [0.42-5.93]	0.026
Bacilli	0.24 [0.15-0.52]	0.54 [0.34-2.1]	0.008
Christensenellaceae	0.12 [000-0.43]	0.43 [0.07-2.59]	0.038
Collinsella	0.04 [0.01-0.05]	0.10 [0.02-0.24]	0.030
Eggerthellaceae	0.04 [0.01-0.06]	0.08 [0.03-0.20]	0.047
Erysipelatoclostridiaceae	0.04 [0.00-0.13]	0.10 [0.05-0.41]	0.015
Erysipelotrichaceae	0.01 [0.00-0.03]	0.05 [0.01-0.11]	0.003
Anaerovoraceceae	0.01 [0.00-0.06]	0.04 [0.01-0.11]	0.027
Hungatella	0.00 [0.00-0.00]	0.01 [0.00-0.04]	0.040
Slackia	0.00 [0.00-0.00]	0.00 [0.00-0.04]	0.008
Peptococcaceae	0.00 [0.00-0.00]	0.00 [0.00-0.02]	0.023
Senegalimassilia	0.00 [0.00-0.00]	0.01 [0.00-0.04];	0.024

Only significant changes in the gut microbiome are indicated.