Probiotics, as common regulators of the gut microbiota, have been used in research to alleviate clinical symptoms of atopic dermatitis (AD).
Objective
Our research team has previously identified a potential relieving effect of Clostridium butyricum on the treatment of AD, but the specific mechanism of how Clostridium butyricum alleviates AD has not yet been confirmed.
Methods
In this study, we explored the relieving effect of Clostridium butyricum on AD through in vivo and in vitro experiments. AD mice induced by 2,4-dinitrofluorobenzene (DNFB) were orally administered with 1 × 108 CFU of Clostridium butyricum for three consecutive weeks.
Results
Oral administration of Clostridium butyricum reduced ear swelling, alleviated back skin lesions, decreased mast cell and inflammatory cell infiltration, and regulated the levels of inflammation-related cytokines. Clostridium butyricum activated the intestinal immune system through the TLR4/MyD88/NF-κB signaling pathway, suppressed the expression of inflammatory factors IL-10 and IL-13, and protected the damaged intestinal mucosa.
Conclusion
Clostridium butyricum administration improved the diversity and abundance of the gut microbiota, enhanced the functionality of the immune system, and protected the epidermal barrier.
Sroka-TomaszewskaJTrzeciakM. Molecular mechanisms of atopic dermatitis pathogenesis. Int J Mol Sci2021; 22: 4130.
2.
WangJMatsukuraSWatanabeS, et al.Involvement of toll-like receptors in the immune response of nasal polyp epithelial cells. Clin Immunol2007; 124: 345–352.
3.
BelderbosMEKnolEFHoubenML, et al.Low neonatal toll-like receptor 4-mediated interleukin-10 production is associated with subsequent atopic dermatitis. Clin Exp Allergy2012; 42: 66–75.
4.
HulsAKlumperCMacIntyreEA, et al.Atopic dermatitis: interaction between genetic variants of GSTP1, TNF, TLR2, and TLR4 and air pollution in early life. Pediat Allerg Imm-Uk2018; 29: 596–605.
5.
YoonJLeyva-CastilloJMWangG, et al.IL-23 induced in keratinocytes by endogenous TLR4 ligands polarizes dendritic cells to drive IL-22 responses to skin immunization. J Exp Med2016; 213: 2147–2166.
6.
LinLXieMChenX, et al.Toll-like receptor 4 attenuates a murine model of atopic dermatitis through inhibition of langerin-positive DCs migration. Exp Dermatol2018; 27: 1015–1022.
7.
YamazakiYNakamuraYNunezG. Role of the microbiota in skin immunity and atopic dermatitis. Allergol Int2017; 66: 539–544.
8.
Lopez-SantamarinaAGonzalezEGLamasA, et al.Probiotics as a possible strategy for the prevention and treatment of allergies. A narrative review. Foods2021; 10: 701.
9.
StokholmJBlaserMJThorsenJ, et al.Maturation of the gut microbiome and risk of asthma in childhood. Nat Commun2018; 9: 141.
10.
KimJEKimHS. Microbiome of the skin and gut in atopic dermatitis (AD): understanding the pathophysiology and finding novel management strategies. J Clin Med2019; 8: 444.
11.
van ZylWFDeaneSMDicksL. Molecular insights into probiotic mechanisms of action employed against intestinal pathogenic bacteria. Gut Microbes2020; 12: 1831339.
12.
LeeJHKaramychevVNKozyavkinSA, et al.Comparative genomic analysis of the gut bacterium Bifidobacterium longum reveals loci susceptible to deletion during pure culture growth. Bmc Genomics2008; 9: 247.
13.
WangKYLiSNLiuCS, et al.Effects of ingesting Lactobacillus- and Bifidobacterium-containing yogurt in subjects with colonized Helicobacter pylori. Am J Clin Nutr2004; 80: 737–741.
14.
SchwiertzATarasDSchaferK, et al.Microbiota and SCFA in lean and overweight healthy subjects. Obesity2010; 18: 190–195.
15.
RabeHLundellACSjobergF, et al.Neonatal gut colonization by Bifidobacterium is associated with higher childhood cytokine responses. Gut Microbes2020; 12: 1–14.
16.
AllenSJWarehamKWangD, et al.Lactobacilli and bifidobacteria in the prevention of antibiotic-associated diarrhoea and Clostridium difficile diarrhoea in older inpatients (PLACIDE): a randomised, double-blind, placebo-controlled, multicentre trial. Lancet2013; 382: 1249–1257.
17.
SilverbergJIHanifinJSimpsonEL. Climatic factors are associated with childhood eczema prevalence in the United States. J Invest Dermatol2013; 133: 1752–1759.
18.
BlunderSRuhlRMoosbrugger-MartinzV, et al.Alterations in epidermal eicosanoid metabolism contribute to inflammation and impaired late differentiation in FLG-mutated atopic dermatitis. J Invest Dermatol2017; 137: 706–715.
19.
OngPYLeungDY. Bacterial and viral infections in atopic dermatitis: a comprehensive review. Clin Rev Allerg Immu2016; 51: 329–337.
20.
HouDDGuYJWangDC, et al.Therapeutic effects of myricetin on atopic dermatitis in vivo and in vitro. Phytomedicine2022; 102: 154200.
21.
FangZLiLZhangH, et al.Gut Microbiota, probiotics, and their interactions in prevention and treatment of atopic dermatitis: a review. Front Immunol2021; 12: 720393.
22.
SuezJZmoraNSegalE, et al.The pros, cons, and many unknowns of probiotics. Nat Med2019; 25: 716–729.
23.
DaleHFRasmussenSHAsillerOO, et al.Probiotics in irritable bowel syndrome: an up-to-date systematic review. Nutrients2019; 11: 2048.
24.
PurushothamanKTanJLauD, et al.Feed restriction modulates growth, gut morphology and gene expression in zebrafish. Int J Mol Sci2021; 22: 1814.
25.
ParkerAFonsecaSCardingSR. Gut microbes and metabolites as modulators of blood-brain barrier integrity and brain health. Gut Microbes2020; 11: 135–157.
26.
BuddenKFGellatlySLWoodDL, et al.Emerging pathogenic links between microbiota and the gut-lung axis. Nat Rev Microbiol2017; 15: 55–63.
27.
StefanovicNFlohrCIrvineAD. The exposome in atopic dermatitis. Allergy2020; 75: 63–74.
28.
SalemIRamserAIshamN, et al.The gut microbiome as a Major regulator of the gut-skin axis. Front Microbiol2018; 9: 1459.
29.
HillCGuarnerFReidG, et al.Expert consensus document. The international scientific association for probiotics and prebiotics consensus statement on the scope and appropriate use of the term probiotic. Nat Rev Gastro Hepat2014; 11: 506–514.
30.
LaiHLiYHeY, et al.Effects of dietary fibers or probiotics on functional constipation symptoms and roles of gut microbiota: a double-blinded randomized placebo trial. Gut Microbes2023; 15: 2197837.
31.
LongMYangSLiP, et al.Combined use of C. butyricum sx-01 and L. salivarius C-1-3 improves intestinal health and reduces the amount of lipids in Serum via modulation of gut Microbiota in mice. Nutrients2018; 10: 810.
32.
ZhangHQDingTTZhaoJS, et al.Therapeutic effects of Clostridium butyricum on experimental colitis induced by oxazolone in rats. World J Gastroentero2009; 15: 1821–1828.
33.
SunJWangFLingZ, et al.Clostridium butyricum attenuates cerebral ischemia/reperfusion injury in diabetic mice via modulation of gut microbiota. Brain Res2016; 1642: 180–188.
34.
HayashiASatoTKamadaN, et al.A single strain of Clostridium butyricum induces intestinal IL-10-producing macrophages to suppress acute experimental colitis in mice. Cell Host Microbe2013; 13: 711–722.
35.
LiHSunJDuJ, et al.Clostridium butyricum exerts a neuroprotective effect in a mouse model of traumatic brain injury via the gut-brain axis. Neurogastroent Motil2018; 30: e13260.
36.
ThomasFHehemannJHRebuffetE, et al.Environmental and gut bacteroidetes: the food connection. Front Microbiol2011; 2: 93.
37.
MagroneTJirilloE. The interplay between the gut immune system and microbiota in health and disease: nutraceutical intervention for restoring intestinal homeostasis. Curr Pharm Design2013; 19: 1329–1342.
38.
ValguarneraEWardenburgJB. Good gone bad: one toxin away from disease for Bacteroides fragilis. J Mol Biol2020; 432: 765–785.
39.
TroyEBKasperDL. Beneficial effects of Bacteroides fragilis polysaccharides on the immune system. Front Biosci-Landmrk2010; 15: 25–34.
40.
CarrowHCBatachariLEChuH. Strain diversity in the microbiome: lessons from Bacteroides fragilis. Plos Pathog2020; 16: e1009056.
41.
WexlerHM. Bacteroides: the good, the bad, and the nitty-gritty. Clin Microbiol Rev2007; 20: 593–621.
42.
De FilippoCCavalieriDDi PaolaM, et al.Impact of diet in shaping gut microbiota revealed by a comparative study in children from Europe and rural Africa. P Natl Acad Sci Usa2010; 107: 14691–14696.
43.
HsiaoEYMcBrideSWHsienS, et al.Microbiota modulate behavioral and physiological abnormalities associated with neurodevelopmental disorders. Cell2013; 155: 1451–1463.
44.
NagalingamNALynchSV. Role of the microbiota in inflammatory bowel diseases. Inflamm Bowel Dis2012; 18: 968–984.
45.
ShaSXuBWangX, et al.The biodiversity and composition of the dominant fecal microbiota in patients with inflammatory bowel disease. Diagn Micr Infec Dis2013; 75: 245–251.
46.
HenrickBMRodriguezLLakshmikanthT, et al.Bifidobacteria-mediated immune system imprinting early in life. Cell2021; 184: 3884–3898.
47.
GroegerDO’MahonyLMurphyEF, et al.Bifidobacterium infantis 35624 modulates host inflammatory processes beyond the gut. Gut Microbes2013; 4: 325–339.
48.
StoevaMKGarcia-SoJJusticeN, et al.Butyrate-producing human gut symbiont, Clostridium butyricum, and its role in health and disease. Gut Microbes2021; 13: 1–28.
49.
HagiharaMKurokiYAriyoshiT, et al.Clostridium butyricum modulates the microbiome to protect intestinal barrier function in mice with antibiotic-induced dysbiosis. Iscience2020; 23: 100772.
50.
HooperLVLittmanDRMacphersonAJ. Interactions between the microbiota and the immune system. Science2012; 336: 1268–1273.
51.
MowatAMAgaceWW. Regional specialization within the intestinal immune system. Nat Rev Immunol2014; 14: 667–685.
52.
KawaiTAkiraS. Toll-like receptors and their crosstalk with other innate receptors in infection and immunity. Immunity2011; 34: 637–650.
XuGRZhangCYangHX, et al.Modified citrus pectin ameliorates myocardial fibrosis and inflammation via suppressing galectin-3 and TLR4/MyD88/NF-kappaB signaling pathway. Biomed Pharmacother2020; 126: 110071.
55.
HuNWangCDaiX, et al.Phillygenin inhibits LPS-induced activation and inflammation of LX2 cells by TLR4/MyD88/NF-kappaB signaling pathway. J Ethnopharmacol2020; 248: 112361.
56.
ChenSNTanYXiaoXC, et al.Deletion of TLR4 attenuates lipopolysaccharide-induced acute liver injury by inhibiting inflammation and apoptosis. Acta Pharmacol Sin2021; 42: 1610–1619.
57.
LuHXuXFuD, et al.Butyrate-producing Eubacterium rectale suppresses lymphomagenesis by alleviating the TNF-induced TLR4/MyD88/NF-kappaB axis. Cell Host Microbe2022; 30: 1139–1150.
58.
XieYZhouLLiH, et al.Clostridium butyricum supernatant regulates the expression of RORgammat in HCT-116 cells by inhibiting the TLR2/MyD88/NF-kappaB signaling pathway. Curr Microbiol2021; 78: 1543–1550.
59.
LiangJKouSChenC, et al.Effects of Clostridium butyricum on growth performance, metabonomics and intestinal microbial differences of weaned piglets. Bmc Microbiol2021; 21: 85.
60.
WangWWWangJZhangHJ, et al.Supplemental Clostridium butyricum modulates lipid metabolism through shaping gut Microbiota and bile acid profile of aged laying hens. Front Microbiol2020; 11: 600.
61.
PellegriniSSordiVBollaAM, et al.Duodenal Mucosa of patients with type 1 diabetes shows distinctive inflammatory profile and Microbiota. J Clin Endocr Metab2017; 102: 1468–1477.
62.
ZhuWLinKLiK, et al.Reshaped fecal gut microbiota composition by the intake of high molecular weight persimmon tannin in normal and high-cholesterol diet-fed rats. Food Funct2018; 9: 541–551.
63.
ParkerBJWearschPAVelooA, et al.The genus Alistipes: gut Bacteria with emerging implications to inflammation, cancer, and mental health. Front Immunol2020; 11: 906.
64.
SungCMLinYFChenKF, et al.Predicting clinical outcomes of cirrhosis patients with hepatic encephalopathy from the fecal microbiome. Cell Mol Gastroenter2019; 8: 301–318.
65.
IebbaVGuerrieriFDi GregorioV, et al.Combining amplicon sequencing and metabolomics in cirrhotic patients highlights distinctive microbiota features involved in bacterial translocation, systemic inflammation and hepatic encephalopathy. Sci Rep-Uk2018; 8: 8210.
66.
LiJSungCYLeeN, et al.Probiotics modulated gut microbiota suppresses hepatocellular carcinoma growth in mice. P Natl Acad Sci Usa2016; 113: E1306–E1315.
67.
IidaNDzutsevAStewartCA, et al.Commensal bacteria control cancer response to therapy by modulating the tumor microenvironment. Science2013; 342: 967–970.
68.
JieZXiaHZhongSL, et al.The gut microbiome in atherosclerotic cardiovascular disease. Nat Commun2017; 8: 845.
69.
KimSGoelRKumarA, et al.Imbalance of gut microbiome and intestinal epithelial barrier dysfunction in patients with high blood pressure. Clin Sci2018; 132: 701–718.
70.
ShenYGiardinoTMLawsonGW, et al.Outer membrane vesicles of a human commensal mediate immune regulation and disease protection. Cell Host Microbe2012; 12: 509–520.
71.
LiuRPengCJingD, et al.Lachnospira is a signature of antihistamine efficacy in chronic spontaneous urticaria. Exp Dermatol2022; 31: 242–247.
72.
FordACQuigleyEMLacyBE, et al.Efficacy of prebiotics, probiotics, and synbiotics in irritable bowel syndrome and chronic idiopathic constipation: systematic review and meta-analysis. Am J Gastroenterol2014; 109: 1547–1561, 1546, 1562.
73.
MayerEATillischKGuptaA. Gut/brain axis and the microbiota. J Clin Invest2015; 125: 926–938.
74.
AshrafRShahNP. Immune system stimulation by probiotic microorganisms. Crit Rev Food Sci2014; 54: 938–956.
75.
CristoforiFDargenioVNDargenioC, et al.Anti-Inflammatory and immunomodulatory effects of probiotics in gut inflammation: a door to the body. Front Immunol2021; 12: 578386.
