Table B1.
Biomarkers that link contributing factors to IBD and immune degradation/COVID-19.
| Contributing Factor | Cat. | Dis. | Biomarkers | Ref. |
|---|---|---|---|---|
| Advanced glycation end products | 1 | IBD | Carboxymethyllysine; enzymatic antioxidative pathways; IL‐6; inflammation; inflammatory cytokine levels; inflammatory response; MDA; Oxidative stress; SOD; TNF‐α | [79] |
| ID | Caspase-1; IL-1; immunosuppressive; innate immune responses; M1 polarization of macrophages; macrophages; NLRP3 inflammasome; pro-inflammatory cytokines in BMDMs; RNA virus infection; type-I interferon | [80] | ||
| COV | Accumulation of advanced glycation end products; acute respiratory distress syndrome; atherothrombotic state; chronic inflammatory; cytokine storm; degrade tissue debris; exaggerated cytokine response; diabetes; impaired immune response; inflammatory response; increased metabolic activity; multi-organ failure; obesity; septic shock; tissue damage; viral infection | [81] | ||
| Alcoholism | 1 | IBD | Crohn Disease (CD); inflammatory bowel disease (IBD); ulcerative colitis (UC) | [82] |
| ID | Alveolar macrophage function; alveolar macrophage immune dysfunction; granulocyte-macrophage colony-stimulating factor receptor; immune dysfunction; intracellular zinc; phagocytic function; zinc bioavailability; zinc deficiency; zinc metabolism | [83] | ||
| COV | Lung fibrosis; pulmonary fibrosis | [84] | ||
| Carrageenan | 1 | IBD | EGR-1; IL-8; intestinal epithelial barrier integrity; Intestinal inflammation; NF-κB; pro-inflammatory transcription factors; UC; zonula occludens | [85] |
| ID | Ccl2; Ccl7; Cxcl1; Cxcl2; inflammatory secretome; leukocyte; macrophages; multiple collagens; neutrophils; peripheral inflammation; tissue inflammation | [86] | ||
| Consumer antimicrobials | 1 | IBD | Colon cancer; colon tumorigenesis; colonic inflammation; IBD; intestinal barrier function; TLR4 signaling | [87] |
| ID | Colon cancer; colon tumorigenesis; colonic inflammation; IBD; intestinal barrier function; TLR4 signaling | [87] | ||
| High-fat diet | 1 | IBD | Cholesterol; colitis; colonic epithelial cells; colonic inflammation; free fatty acids; gp91; IBD; lamina propria cells; MLCK tight junction; mucosal barrier permeability; mucosal oxidative stress; mucosal pro-inflammatory cytokines; ROS; triglyceride | [88] |
| ID | Gut-associated lymphoid tissue; IBD; lamina propria lymphocytes; lipotoxicity; small intestinal intraepithelial lymphocytes | [89] | ||
| COV | Endotoxemia; gut microbiome dysbiosis; immunosilent/immunoinhibitory bacteroidetes LPS; intestinal permeability; lipopolysaccharide (LPS); oxidative stress; proinflammatory LPS; TLR4 | [90] | ||
| High-salt diet | 1 | IBD | activated peritoneal macrophages; CD11b + macrophages; CD3+CD4+CD25+Foxp3+ T cells; CD4+IFN-γ+IL-17+ T cells; colitis; IFN-γ; IL-1; IL-10; IL-6; lamina propria; lamina propria mononuclear cells; macrophages; mesenteric lymph node; mouse inducible nitric oxide synthase; p38 phosphorylation; p38/MAPK axis; peritoneal macrophage inflammation; proinflammatory; SGK1; spleen; TGF-β; Th1; Tregs | [91] |
| ID | Autoimmune disease; inflammatory disease; inflammatory kidney disease; innate and adaptive immune systems; innate immune system components | [92] | ||
| Malnutrition | 1 | IBD | Catalase (CAT); colon epithelium; IL-1β; IL-4; inflammatory mediators; lipoperoxidation; NO; oxidative stress; reduced (GSH) and oxidized (GSSG) glutathione; TNF-α; total superoxide dismutase (tSOD) | [93] |
| ID | chronic inflammation; disordered nutrient assimilation; immune defect; immune dysfunction; immunopigenome; infections | [94] | ||
| COV | cytokine storm; high adiposity; infection; low lean mass; proinflammatory cytokines | [95] | ||
| Maternal smoking | 1 | IBD | cg25189904 in GNG12 gene; DNA methylation | [96] |
| ID | Asthma; cotinine; respiratory infections; toll-like-receptor (TLR) | [97] | ||
| COV | COVID-19 | [98] | ||
| Nitrosamines | 1 | IBD | chronic inflammation; hydrogen peroxide; mutagenesis; nitrosation; N-nitrosamine derivatives; NO; oxidation; ROS; secondary amines; superoxide; UC | [99] |
| ID | Arachidonic acid metabolites; IgG; leukotrienes; N-nitrosamines (N-nitrosodimethylamine and N-nitrosodiethylamine); oncosuppression; p53 transcription factor | [100] | ||
| Polysorbate-80 | 1 | IBD | Endoplasmic reticulum stress; gut homeostasis; IL-10; immune-inflammatory disorders; IBD; inflammatory responses; intestinal goblet cells; TLR5 | [101] |
| ID | sensitization rates | [102] | ||
| Refined carbohydrates | 1 | IBD | CD; DNA methylation; histone modification; IBD; miRNAS; UC | [103] |
| ID | Adaptive immunity; chronic inflammation; impaired host defense; innate immune system; peripheral inflammation | [104] | ||
| COV | Chronic inflammation; COVID-19; dementia; impairs adaptive immunity; impaired host defense; innate immune system; neurodegenerative disease; neuroinflammatory; type 2 diabetes; obesity; peripheral inflammation | [104] | ||
| Sedentary | 1 | IBD | Adipokines; colonic blood flow (CBF); colonic microcirculation; COX-2; disease activity index; GPx mRNAs; hypoxia inducible factor (HIF)-1α; IFNγ; IL-10; IL-17; IL-1β; IL-6; iNOS; intestinal microcirculation; MDA; myokines; oxidative stress; reduced glutathione (GSH); SOD-1; SOD-2; SOD; TNF-α; weight | [105] |
| ID | Atherosclerosis; cytokines; development of tumors; immune cells with pro-inflammatory characteristics in adipose tissue; insulin resistance; neurodegeneration | [106] | ||
| COV | Body mass index; obesity; severe infection | [107] | ||
| Vitamin D deficiency | 1 | IBD | Anti-inflammatory; autoimmune diseases; cathelicidin; DEFB4 (defensin, beta 4); gastrointestinal inflammation; gut microbiome | [108] |
| ID | Acetylcholine; actinobacteria; autoimmune arthritis; bacteroidetes; pantothenic acid deficiency; bowel symptoms; cortisol; firmicutes; pain; proteobacteria; sleep; vitamin D blood levels | [109] | ||
| COV | cytokine storm; dengue fever; innate immune system; virus replication; vitamin D deficiency | [110] | ||
| Antibiotics | 2 | IBD | CD; IBD; UC | [111] |
| ID | Adaptive immunity; immune responses; infection; microbiota homeostasis | [112] | ||
| Cisplatin | 2 | IBD | Anorexia; bloody stool; colitis; diarrhea; UC | [113] |
| ID | Humoral immunity; immunotoxicity; leukocytic count; lymphocyte percentage; lymphoid tissue; mycoplasma gallisepticum; neutrophil percentage; phagocytic activity; total protein; γ-globulin concentration | [114] | ||
| Opioids/Morphine | 2 | IBD | ATP release; ATP-induced currents; bacterial translocation; colonic inflammation; connexin43 (Cx43); enteric glia; IL-1β mRNA; IL-6; leaky gut; microbial dysbiosis; P2X currents; P2 × 4; P2 × 7; purinergic P2X receptor activity | [115] |
| ID | Acetylcholinesterase; AP-1; bone marrow-derived macrophages; CREB; innate immunity; microglia; microRNA-124; NF-κB p65; pain; phospho-p65; TLRs; TNFR-associated factor 6 | [116] | ||
| COV | COVID-19 | [117] | ||
| Oral contraceptives | 2 | IBD | UC | [118] |
| ID | Autoimmune diseases; blood urea nitrogen; cytokines; glomerular immune complex deposition; immune system; kidney disease; proteinuria; splenic leukocytes; TLR7/9 cytokine production | [119] | ||
| Radiotherapy | 2 | IBD | Bloating/distension; chronic gastrointestinal symptoms; fecal incontinence; flatulence; frequency; loose stool; rectal bleeding; urgency | [120] |
| ID | Blood proteome; inflammatory responses | [121] | ||
| COV | Cancer; carcinoma; COVID-19 | [122] | ||
| Renal transplantation | 2 | IBD | Diarrhea; diverticular colon disease; fecal occult blood; gastrointestinal pathologies; HBoV; HBoV-3; immunosuppressed; RVA; RVA G3 | [123] |
| ID | Diarrhea; Rotavirus A (RVA) and Human Bocavirus (HBoV) in fecal samples | [124] | ||
| COV | Chronic kidney disease; infection | [125] | ||
| Rituximab | 2 | IBD | Autoimmune disease; CD20 + lymphocytes; CD; granulomas; granulomas; ileocolitis; inflammation; inflammation; ulceration; ulceration; UC | [126] |
| ID | Hypogammaglobulinemia; IgG; severe infections | [127] | ||
| COV | Bilateral pneumonia; respiratory insufficiency; rheumatic and musculoskeletal disease; rheumatoid arthritis; SAR-CoV-2 infection; Sjögren syndrome; systemic lupus erythematosus; systemic vasculitis | [128] | ||
| Vaccines | 2 | IBD | IBD | [129] |
| ID | Non-influenza infections | [130] | ||
| Cytomegalovirus | 3 | IBD | Autoantibodies; autoimmune; CD13 (aminopeptidase N); CD13 (aminopeptidase N) specific autoantibodies; human cytomegalovirus infection | [131] |
| ID | Autoimmune diseases; HCV; immune dysfunction; immunosuppression; inflammation | [132] | ||
| COV | Cytomegalovirus (CMV); herpesvirus infection; immune senescence; infection; metabolic disorders | [133] | ||
| N-ethyl-N-nitrosourea | 3 | IBD | Apoptosis; chronic diarrhoea; endoplasmic reticulum stress; IFN-γ; IFN-γ; IL-13; IL-1β; inflammation; intestinal mucus barrier; intestinal goblet cells; intestinal permeability; leukocytes; MUC2 mucin; Th1 cytokines; Th2 cytokines; TNF-α; ulcerative colitis-like phenotype; unfolded protein response | [134] |
| ID | Cell surface receptors; innate immunity; toll-like receptors | [135] | ||
| Trichothecenes | 3 | IBD | Caco-2 cell monolayer; celiac disease; chronic IBD; claudin protein levels; claudins; colonic epithelial barrier; FITC-dextran; ZO-1 | [136] |
| ID | B cells; chemokines; cytokines; double-stranded RNA-(dsRNA)-activated protein kinase; hematopoetic cell kinase (Hck); immune suppression; immune system; inflammatory genes; leukocyte apoptosis; macrophages; MAPKs; T-cells | [137] | ||
| Zearalenone | 3 | IBD | Autoimmune; IFN-γ; IgE; IL-2; infectious diseases; macrophages; monocytes; proinflammatory cytokines; Th1 cytokines; Th1/Th2 cell polarization; Th2 cytokines; ZEN concentrations | [138] |
| ID | Autoimmune; IFN-γ; IgE; IL-2; infectious diseases; macrophages; monocytes; proinflammatory cytokines; Th1 cytokines; Th1/Th2 cell polarization; Th2 cytokines; ZEN concentrations | [138] | ||
| Air pollutants | 4 | IBD | Epithelial cells; immune activation; intestinal microbiota; systemic inflammation | [139] |
| ID | IgG; IgM; monocytes; red blood cells; white blood cells | [140] | ||
| COV | COVID-19 | [141] | ||
| Aluminum | 4 | IBD | Colitis; colonic myeloperoxidase activity; epithelial cell renewal; granuloma formation; immune toxicity; inflammatory cytokines expression; intestinal barrier function; intestinal inflammation | [142] |
| ID | ANAE(+) cells; complement 3 (C3) level; IL-2; immunotoxicity; splenic iron; splenic zinc; TNF-α | [143] | ||
| Benzene | 4 | IBD | Abdominal pain; bloody diarrhea; CD11b + cell infiltration; colonic migrating motor complex frequency and amplitude; cramping; epithelial barrier permeability; IL-1β concentrations; inflammation; innate immune activation; migrating CD11b + cells | [144] |
| ID | ALA-D activity; CD80; CD86; IL-8; lymphocytes; monocytes | [145] | ||
| COV | COVID-19 | [146] | ||
| Benzo(a)pyrene | 4 | IBD | Colonic mucosa; gut microbiota dysbiosis; intestinal inflammation; lesions | [147] |
| ID | IgM; lysosomal membrane stability; lysozyme activity; phagocytosis; total RBC and WBC | [148] | ||
| Bisphenol | 4 | IBD | IBDs; oral tolerance; pro-inflammatory cellular responses | [149] |
| ID | Anti-E. coli IgG; immune response; inflammatory markers; intestinl barrier functions; Th1/Th17 inflammation | [150] | ||
| COV | Angiotensin-converting enzyme 2; GPR30; infection; membrane-bound oestrogen receptor; nuclear oestrogen receptors; nuclear receptor oestrogen-related receptor gamma; transmembrane serine protease 2 | [151] | ||
| Cadmium | 4 | IBD | Bacteria-induced cytokine responses; gastrointestinal autoimmune diseases; IBD; intestinal inflammation; transepithelial electric resistance | [152] |
| ID | Apoptosis induction; glutathione; IgE-mediated histamine release; immunotoxic; innate immune system; macrophages; mast cells; nitrite production; oxidative stress; ROS; redox imbalance; TNF-α | [153] | ||
| COV | Adaptive immunity; airway inflammation; apoptosis; barrier function; immunotoxicity; mucociliary clearance; oxidative stress | [154] | ||
| Chlorpyrifos | 4 | IBD | Chronic inflammation; colon weights; haptoglobin; immune tolerance; luminal IgG levels; neutrophils; Treg cells; spleen T cells; T-cells; Treg-related genes; TNF-α | [155] |
| ID | Immune response; oxidative stress; ROS | [156] | ||
| Fluoridated water | 4 | IBD | Gut microbiota; intestinal inflammation | [157] |
| ID | Catalase; cellular immunity; humoral immunity; immunotoxicity; MDA; monocytes; neutrophils; oxidative stress; peripheral blood lymphocytes; peroxidase; plasma IgG; spleen; splenocytes counts; thymus | [158] | ||
| Mercury | 4 | IBD | UC | [159] |
| ID | Humoral immune response; IgE | [160] | ||
| COV | Airway inflammation; apoptosis; immunotoxicity; impaired mucociliary clearance; influenza; oxidative stress; reduced barrier function; respiratory diseases (COPD, bronchitis); respiratory dysfunction; respiratory syncytial virus; viral diseases | [154] | ||
| Microplastics | 4 | IBD | Dysbiosis; gut epithelium; gut's epithelial permeability; immune cell toxicity; immune response; inflammatory intestinal balance; intestinal homeostasis; microbiota | [161] |
| ID | Dysbiosis; gut epithelium; gut's epithelial permeability; immune cell toxicity; immune response; inflammatory intestinal balance; intestinal homeostasis; microbiota | [161] | ||
| Nickel | 4 | IBD | Metal hypersensitivity; T-cells; ulcerative lesions | [162] |
| ID | Apoptosis; cytokines; development of immune organs; immunoglobulins; immunotoxicity; immunotoxicological; inflammation; inflammation; lymphocyte; macrophages; natural killer cells; nuclear factor-κB; MAPK pathways; T and B lymphocytes; toll like (TL)4 | [163] | ||
| Paraquat | 4 | IBD | IBD; sulfide; ulcerative colitis | [164] |
| ID | Apoptosis; apoptosis of lymphocytes; immunotoxicity; memory cells; memory immune response; number of effector and memory lymphocytes; primary immune response; secondary immune response; serum total IgG; serum anti-KLH IgG and KLH-responsive CD4 T cells and B cells | [165] | ||
| PCB (polychlorinated biphenyls) | 4 | IBD | Catalase; free radical production; GSH-Px; high-molecular-weight antioxidants; low-molecular-weight antioxidants; lymphocytes; neutrophils; oxidative injuries; SOD; vitamin A; vitamin C; vitamin E | [166] |
| ID | Leukocyte phagocytosis | [167] | ||
| PFOA (perfluoroctanoic acid) | 4 | IBD | CD; PFAS serum levels; PFOS serum levels; UC | [168] |
| ID | IL-1β; IL-21; Myd88/NF-κB pathway; myeloid differentiation 88; P65 transcription factor; pro-inflammatory cytokine IL-1β; spleen; TLR2 | [169] | ||
| COV | Immunotoxic; PFAS concentrations; perfluorobutanoic acid (PFBA); short-chain PFBA | [170] | ||
| Polycyclic aromatic hydrocarbons | 4 | IBD | Abnormal cell growth; barrette's esophagus; blood circulation; cell dysfunction; chronic inflammation; CDs; DNA adducts; gene mutation; neural regulation; ulcer formation; SOD; UC | [171] |
| ID | Antibody-forming cell response; immunosuppression; immunotoxicity | [172] | ||
| COV | Adverse respiratory effects; COVID-19; severe respiratory infections | [173] | ||
| Silica dust | 4 | IBD | CD; UC | [174] |
| ID | autophagy; Bcl-2; Beclin1; macrophages; NR8383 cells; PIK3C3 | [175] | ||
| COV | HIV; Interstitial lung disease; Silicosis; tuberculosis (TB) | [176] | ||
| Sodium dichromate dihydrate | 4 | IBD | Bile acid concentrations; body weights; epithelial hyperplasia; erythrocyte counts; focal ulceration; glycogen depletion; histiocytic cellular infiltration; mean red cell volumes; microcytic hypochromic anemia; nonneoplastic lesions; red cell hemoglobin values; serum cholesterol; triglyceride; urine specific gravity; urine volume | [177] |
| ID | Alveolar macrophages; antibody responses; humoral immune system; phagocytic activities | [178] | ||
| COV | Arsenic; cadmium; chromium; copper; creatinine; inflammatory; ferritin; lead; manganese; mercury; neutrophil count; selenium; serum cytokines (IL-1B, IL-2R, IL-6, IL-8, IL-10, TNFα); thallium; toxic metals; trace metals; urinary creatinine-adjusted copper; white blood cell count | [179] | ||
| Titanium dioxide | 4 | IBD | Body mass; dysbiosis; GI microbiome; immune response; inflammation; inflammatory cytokines; mucin expression; mucosal barrier; mucus production | [180] |
| ID | Immunomodulation; immunosuppressant; splenocytes proliferation; T-cell; Th1 type cytokines (IL-2, interferon-γ) | [181] | ||
| Triclocarban | 4 | IBD | Colitis; gut microbiota | [182] |
| ID | Cxcl-clc; IL-1β; IL-4; IL-8; immune cell recruiting; irak4; lipid peroxidation; myd88; NF-κB; NO; NO synthase gene; oxidative damage; oxidative stress; SOD; TNF-α; total antioxidant capacity expression; traf6; trif | [183] | ||
| Turpentine | 4 | IBD | Colonic distension; NMDA receptor; visceral pain | [184] |
| ID | Concanavalin A; IgG; inflammation; IL-6 | [185] | ||
| Low socioeconomic status | 5 | IBD | Autoimmune disorders; CD | [186] |
| ID | Adverse events following immunization | [187] | ||
| COV | COVID-19 | [188] | ||
| Posttraumatic stress | 5 | IBD | Autoimmune disorders; immune abnormalities; rheumatoid arthritis | [189] |
| ID | Dysregulation of genes; innate immune; NF-κB | [190] | ||
| Psychological stress | 5 | IBD | Intestinal permeability; mast cells activation; salivary cortisol | [191] |
| ID | Cytokines; IFN-γ; IL-1β; IL-10; IL-6; immune cell populations; immune function; macrophage; Th1 cell-mediated cellular immunity; Th2 cell-mediated humoral immunity and macrophage activities; Th1 cell; Th2 cell | [192] | ||
| COV | Cytokine storm; diabetes; glucocorticoid insufficiency; hyperinflammation; hyperinflammatory responses; hypertension; immune dysregulation; inflammation; IL-6 hypersecretion; lung conditions; obesity | [193] | ||
| Restraint stress | 5 | IBD | Colonic mucin glycoprotein; goblet cells; mast cell counts; mucin; myeloperoxidase content | [194] |
| ID | CD4+ T lymphocytes; CD8 + T lymphocytes; cytokine levels; IL-10; IL-17; IL-6; immunosuppression; splenic natural killer cell activity; splenocyte proliferation | [195] | ||
| Sexual abuse | 5 | IBD | CD; IBD; Irritable bowel syndrome; UC | [196] |
| ID | C-reactive protein; IL-6; inflammatory activity; inflammatory responses; TNF-α | [197] |