Gut dysbiosis and systemic inflammation promote cardiomyocyte abnormalities in an experimental model of steatohepatitis

Table 1 Atherogenic ratios, inflammation and endothelial dysfunction markers in a nutritional model of steatohepatitis

Variable	Control (n = 10)	Intervention (n = 10)	P value
AC	0.6 (0.2–0.9)	2.5 (1.5–3.4)	< 0.001a
CRI-I	1.6 (± 0.4)	3.5 (± 1.1)	< 0.001a
CRI-II	0.3 (± 0.1)	0.8 (± 0.2)	< 0.001a
IL-1β (pg/mL)	367.7 (± 31.2)	465.9 (± 52.7)	0.001a
MCP-1 (ng/mL)	2.7 (± 0.6)	3.8 (± 0.9)	0.005a
TIMP-1 (ng/mL)	7.1 (± 1.4)	12.4 (± 2.3)	< 0.001a
PAI-1 (ng/mL)	0.11 (± 0.05)	0.17 (± 0.06)	0.037a

Data are means ± standard deviation or medians (25^th-75^th percentiles).

^aP ≤ 0.05 was considered statistically significant.

AC: Atherogenic coefficient; CRI: Castelli’s risk index; IL: Interleukin; MCP: Monocyte chemoattractant protein; PAI: Plasminogen activator inhibitor; TIMP: Tissue inhibitor of metalloproteinase.

Table 2 Correlation of steatohepatitis, cardiovascular risk, and microbiota composition

Variable1		Severity and progression of liver injury				CVR factors and metabolism of lipids						Cardiomyocyte morphometry			Microbiota composition
		Quantification of collagen (picrosirius)	TIMP-1	MCP-1	IL-1β	miR-33a	miR-126	PAI-1	CRI-I	CRI-II	AC	% Normal CAR	Average area of CAR	% Atrophic CAR
Severity and progression of liver injury	NAFLD score	0.8792	0.7912	0.6732	0.347	0.6392	-0.7772	0.4443	0.8092	0.8202	0.8092	-0.5193	-0.6302	0.7212	0.6942
	Quantification of collagen (picrosirius)		0.6112	0.4563	0.7522	0.5713	-0.6832	0.415	0.8192	0.8212	0.8192	-0.205	-0.312	0.238	0.3782
	TIMP-1			0.8032	0.7262	0.7282	-0.8122	0.5353	0.6912	0.7472	0.6912	-0.6942	-0.405	0.6072	0.5392
	MCP-1				0.5673	0.4923	-0.6232	0.336	0.5493	0.5613	0.5493	-0.4903	-0.390	0.4983	0.2323
	IL-1β					0.8092	-0.6883	0.5443	0.6453	0.6882	0.6453	-0.4373	-0.393	0.382	0.2933
CVR factors and metabolism of lipids	miR-33a						-0.6552	0.363	0.5293	0.6033	0.5293	-0.7042	0.038	0.232	0.1603
	miR-126							-0.6342	-0.7122	-0.7302	-0.7122	0.4593	0.320	-0.364	0.3682
	PAI-1								0.4873	0.6712	0.4873	-0.317	0.389	-0.289	0.103
	CRI-I									0.8632	1.0002	-0.234	-0.4593	0.386	0.4692
	CRI-II										0.8632	-0.399	-0.4923	0.5513	0.5842
	AC											-0.236	-0.4573	0.389	0.4772
Cardiomyocyte morphometry	% Normal cardiomyocytes												0.105	-0.058
	% Average area of cardiomyocytes													-0.8182
	% Atrophic cardiomyocytes

¹Variables were evaluated by Spearman's r correlation coefficient: moderate (0.3 < r < 0.6), strong (0.6 < r < 0.9) or very strong (0.9 < r < 1.0).

²Correlation significant at the 0.01 level.

³Correlation significant at the 0.05 level.

AC: Atherogenic coefficient; CAR: Cardiomyocytes; CRI: Castelli’s risk index; CVR: Cardiovascular risk; IL: Interleukin; MCP: Monocyte chemoattractant protein; NAFLD: Nonalcoholic fatty liver disease; PAI: Plasminogen activator inhibitor; TIMP: Tissue inhibitor of metalloproteinase.

Table 3 Correlation of gut microbiota at family level, steatohepatitis, and cardiovascular risk factors

Variable1 (Family)	Severity and progression of liver injury				CVR factors and metabolism of lipids
	NAFLD score	Quantification of collagen (picrosirius)	TIMP-1	MCP-1	miR-33a	miR-126	PAI-1	CRI-I	CRI-II	AC
Actinomycetaceae					0.5842
Aerococcaceae
Anaeroplasmataceae		-0.5532						-0.6142		-0.6142
Atopobiaceae	0.6272	0.6102						0.5922	0.6632	0.5922
Bacillales_unclassified						0.5492		-0.5482	-0.5332	-0.5482
Bacteroidaceae	0.8362	0.7462	0.7842		0.6892	-0.7542		0.6622	0.7322	0.6622
Bacteroidales_unclassified		-0.5602							-0.5892	-0.4922
Burkholderiaceae									0.5642
Clostridiaceae	0.8072	0.7232	0.6452		0.5932	-0.6692		0.6762	0.6382	0.6762
Clostridiales_unclassified	-0.6282	-0.5292	-0.5352		-0.5762				-0.5862	-0.5252
Clostridiales_vadinBB60	-0.6022	-0.6712	-0.5272		-0.5582	0.5242		-0.6262	-0.5022	-0.6262
Corynebacteriaceae	-0.6692	-0.5452	-0.6802		-0.7822	0.6112		-0.5712	-0.6222	-0.5712
Desulfovibrionaceae	-0.8062	-0.6032	-0.8722	-0.7762	-0.6312	0.7552		-0.7292	-0.7462	-0.7292
Eggerthellaceae									0.4902
Firmicutes_unclassified	-0.7972	-0.6372	-0.6872		-0.6552	0.5942		-0.6292	-0.6992	-0.6292
Gastranaerophilales	-0.8222	-0.6562	-0.6442		-0.6432	0.6572		-0.6982	-0.5862	-0.6982
Lachnospiraceae	-0.8502	-0.6532	-0.7892	-0.7882	-0.6132	0.7662		-0.6432	-0.6292	-0.6432
Lactobacillaceae	-0.6162	-0.6332				0.7952			-0.5292
Lactobacillales_unclassified
Micrococcaceae	0.6692		0.5342			-0.5282			0.4932
Mollicutes_RF39_fa	-0.6502	-0.6182	-0.5902		-0.6092	0.7132		-0.8572	-0.7682	-0.8572
Moraxellaceae	-0.6692	-0.5362	-0.5572		-0.5432			-0.5992	-0.4732	-0.5992
Muribaculaceae	-0.8162	-0.7942			-0.5762	0.6932	-0.6842	-0.8272	-0.8462	-0.8272
Pasteurellaceae
Prevotellaceae		-0.7052				0.6032			-0.5222	-0.4862
Rikenellaceae					-0.6792
Saccharimonadaceae	-0.7372	-0.5592	-0.6192		-0.6742	0.6562		-0.7762	-0.7592	-0.7762
Staphylococcaceae	-0.7342	-0.6472	-0.8082		-0.8382	0.7162		-0.6162	-0.6792	-0.6162
Streptococcaceae	0.7902	0.7262	0.6372		0.5952	-0.6222			0.7242	0.5152

¹Variables were evaluated by Spearman's r correlation coefficient, moderate (0.3 < r < 0.6) or strong (0.6 < r < 0.9).

²Correlation significant at the 0.05 level.

AC: Atherogenic coefficient; CRI: Castelli’s risk index; CVR: Cardiovascular risk; MCP: Monocyte chemoattractant protein; NAFLD: Nonalcoholic fatty liver disease; PAI: Plasminogen activator inhibitor; TIMP: Tissue inhibitor of metalloproteinase.