Gut microbiome in acute pancreatitis: A review based on current literature

Table 1 Revised Atlanta classification and determinant-based classification of acute pancreatitis

Revised Atlanta classification of disease severity
Mild AP	No organ failure
	No local or systemic complications
Moderately severe AP	Organ failure that resolved within 48 h (transient organ failure) and /or
	Local or systemic complications without persistent organ failure
Severe AP	Persistent organ failure > 48 h
	Single organ failure
	Multiple organ failure
A modified Marshal score defines a persistent organ failure
Determinant-based classification of disease severity
RACAP	DBCAPS
Mild AP	Mild AP
Absence of organ failure	Absence of organ failure
Absence of local complications	Absence of (peri-) pancreatic necrosis
Moderately severe AP	Moderate AP
Local complications and/or	Sterile (peri-) pancreatic necrosis and/or
Transient organ failure	Transient organ failure
Severe AP	Severe AP
Persistent organ failure	Persistent organ failure or
	Infected (peri-) pancreatic necrosis
	Critical AP persistent organ failure
	Infected (peri-) pancreatic necrosis

AP: Acute pancreatitis; DBCAPS: Determinant-based classification of acute pancreatitis severity; RACA: Revised Atlanta classification. Persistent organ failure is defined by a modified Marshal score or a sepsis-related organ failure assessment score.

Table 2 Prediction scoring systems used in acute pancreatitis diagnosis

No.	Multifactorial scoring system	Timeline	Threshold	Area under the curve	Ref.
1	Ranson score	48 h	≥ 3	0.81–0.88	[33-35]
2	Glasgow score	48 h	2	0.73–0.784	[36,37]
3	Acute Physiology and Chronic Health Evaluation-II score (APACHE-II)	24 h	7	0.80–0.895	[33,38,39]
4	Acute Physiology and Chronic Health Evaluation II score-Obesity (APACHE:-O)	24 h	7	0.893	[40]
5	Bedside Index of Severity score (BISAP)	24 h	≥ 3	0.79–0.875	[33-35,41]
6	Pancreatitis Activity Scoring System (PASS)	24 h	> 160	0.71	[36]
7	Systemic inflammatory response syndrome (SIRS)	24 h	≥ 2	0.73	[34,39]

Table 3 Blood biomarkers predicting disease severity in acute pancreatitis

No.	Blood biomarkers	Timeline	Threshold	Area under the curve	Ref.
1	Interleukin 8	Preoperative	196 pg/mL	0.778	[42]
2	Interleukin 6	24 h	50 pg/mL	0.9	[39]
3	Hepcidin	24 h	234.4 ng/mL	0.82	[43]
4	Red blood cell distribution width	24 h	13.35%	0.787	[44]
5	Procalcitonin	24 h	1.77 ng/mL	0.797	[45]
6	Blood urea nitrogen	24 h	5.945 mg/dL	0.677	[44]
7	Oleic acid chlorohydrin	24 h	32.40 nM	1	[46]
8	C-reactive protein	24 h	150 mg/L	0.61	[47]
9	C-reactive protein	48 h	150 mg/L	0.73–0.91	[33,39,47]

Table 4 MicroRNAs used as biomarkers in the diagnosis of acute pancreatitis

No.	miRNAs	Patients	Sample	Expression change	Reference gene	Ref.
1	miR-216a	AP	Plasma	Up	None	[49]
2	miR-551b-5p	AP	Plasma	Up	miR-16	[50]
3	miR-216a-5p, miR-375, and miR-551b-5p	AP	Serum	Up	miR-103a-3p	[51]
4	miR-7, miR-9, miR-122, and miR-141	AP	Serum	Up	Exogenous reference genes	[52]
5	miR-216a	AP	Plasma	Up	U6	[53]
6	miR-551-5p	AP	PBMC-	Up	U6	[54]
7	miR-155	AP	Serum	Up	U6	[55]
8	miR-29a	AP	Plasma	Up	U6	[56]
9	miR-24-3p, miR-222-3p, miR-361-5p, and miR-1246	HTG-AP	Serum	Up	U6	[57]
10	miR-1260b, miR-762, miR-22-3p, miR-23b, and miR-23a	AP-associated ALI	Serum	Up	U6	[58]
11	miR-92b, miR-10a, and miR-7	AP	Plasma	Down	miR-16	[50]
12	miR-155	AP	Serum	Down	Not mentioned	[59]
13	miR-181a-5p	HTG-AP	Serum	Down	U6	[57]
14	miR-550a, miR-324-5p, miR-484, miR-331-3p, miR-140-3p, miR-342-3p, and miR-150	AP-associated ALI	Serum	Down	U6	[58]
15	miR-127	AP-associated ALI	Plasma	Down	miR-16	[60]

ALI: Acute lung injury; AP: Acute pancreatitis; HTG-AP: Hypertriglyceridemic-acute pancreatitis; mi: Micro.

Table 5 Altered microbiome composition in acute pancreatitis vs healthy controls

No.	Techniques used for microbiome profiling	Healthy control	Acute pancreatitis	Ref.
1	qPCR (Fecal samples)	Firmicutes↑	Firmicutes↓	[84]
		Bacteroidetes↓	Bacteroidetes↑
		Proteobacteria↓	Proteobacteria↑
		Actinobacteria↑	Actinobacteria↓
		Tenericutes↓	Tenericutes↑
2	16S rRNA gene sequencing (Fecal samples)	Proteobacteria↓	Bacteroidetes↓	[83]
			Proteobacteria↑
			Escherichia/Shigella↑
			Enterococcus↑
			Enterobacteriaceae↑
			Prevotella↓
			Faecalibacterium↓
			Bifidobacterium↓
3	16S rRNA gene sequencing (Fecal samples)	NA	Bacteroidetes↑	[85]
			Proteobacteria↑
			Firmicutes↓
			Actinobacteria↓
4	16S rRNA gene sequencing (Fecal samples)	NA	Enterobacteriaceae↑	[21]
			Enterococcus↑
			Bifidobacteria↓

NA: Not available. ↑: Higher level; ↓: Lower level.

Table 6 Altered microbiome composition observed in acute pancreatitis of increasing severity

No.	Techniques used for microbiome profiling	MAP	MSAP	SAP	Ref.
1	qPCR (Fecal samples), performed only on MAP and SAP patients	Enterococcus↑	NA	Enterococcus↑	[79]
		Enterobacteriaceae↑		Enterobacteriaceae↑
		Bifidobacterium↓		Bifidobacterium↓
2	16S rRNA gene sequencing (Fecal samples)	Finegoldia↑	NA	Acinetobacter↑	[83]
				Stentrophomonas↑
				Geobacillus↑
				Bacteroides↓
				Alloprevotella↓
				Blautia↓
				Gemella↓
3	16S rRNA sequencing (Fecal sample)	Enterobacteriaceae↑	NA	Enterobacteriaceae↑	[85]
		Enterococcus↑		Enterococcus↑
		Bifidobacterium↓		Bifidobacterium↓
				Blautia↓
4	16S rRNA gene sequencing (Rectal swab)	Bacteroides↑	Bacteroides↑	Bacteroides↑	[82]
		Escherichia/Shigella↑	Escherichia/Shigella↑	Escherichia/Shigella↑
		Enterococcus↑	Enterococcus↑	Enterococcus↑
				Eubacterium hallii↓
		Finegoldia↑	Anaerococcus↑	Acinetobacter↓
				Stenotrophomonas↓
		Blautia↓	Eubacterium hallii↓	Bacteroides↓
				Blautia↓
5	Shotgun metagenomics (Fecal sample)	Thermoprotei↑	Sulfolobus↑	Sulfolobus↑	[86]
		Crenarchaeota↑	Methanobrevibacter ruminantium↑	Methanomicrobiales - archaeon 53_19↑
		Streptococcus↑	Methanosarcina - Thermophila↑	Enterococcus↑
		Anaerostipes hadrus↓	Anaerostipes hadrus↓	Blautia↓
			Escherichia coli↑

MAP: Mild acute pancreatitis; MSAP: Moderately severe acute pancreatitis; NA: Not available; SAP: Severe acute pancreatitis; ↑: Higher level; ↓: Lower level.