Tags

Type your tag names separated by a space and hit enter

Anti-tumor necrosis factor α therapy associates to type 17 helper T lymphocytes immunological shift and significant microbial changes in dextran sodium sulphate colitis.
World J Gastroenterol. 2019 Mar 28; 25(12):1465-1477.WJ

Abstract

BACKGROUND

Anti-tumor necrosis factor α (TNFα) represents the best therapeutic option to induce mucosal healing and clinical remission in patients with moderate-severe ulcerative colitis. On the other side gut microbiota plays a crucial role in pathogenesis of ulcerative colitis but few information exists on how microbiota changes following anti-TNFα therapy and on microbiota role in mucosal healing.

AIM

To elucidate whether gut microbiota and immune system changes appear following anti TNFα therapy during dextran sulfate sodium (DSS) colitis.

METHODS

Eighty C57BL/6 mice were divided into four groups: "No DSS", "No DSS + anti-TNFα", "DSS" and "DSS + anti-TNFα". "DSS" and "DSS + anti-TNFα" were treated for 5 d with 3% DSS. At day 3, mice whithin "No DSS+anti-TNFα" and "DSS+anti-TNFα" group received 5 mg/kg of an anti-TNFα agent. Forty mice were sacrificed at day 5, forty at day 12, after one week of recovery post DSS. The severity of colitis was assessed by a clinical score (Disease Activity Index), colon length and histology. Bacteria such as Bacteroides, Clostridiaceae, Enterococcaceae and Fecalibacterium prausnitzii (F. prausnitzii) were evaluated by quantitative PCR. Type 1 helper T lymphocytes (Th1), type 17 helper T lymphocytes (Th17) and CD4+ regulatory T lymphocytes (Treg) distributions in the mesenteric lymph node (MLN) were studied by flow cytometry.

RESULTS

Bacteria associated with a healthy state (i.e., such as Bacteroides, Clostridiaceae and F. prausnitzii) decreased during colitis and increased in course of anti-TNFα treatment. Conversely, microorganisms belonging to Enterococcaceae genera, which are linked to inflammatory processes, showed an opposite trend. Furthermore, in colitic mice treated with anti-TNFα microbial changes were associated with an initial increase (day 5 of the colitis) in Treg cells and a consequent decrease (day 12 post DSS) in Th1 and Th17 frequency cells. Healthy mice treated with anti-TNFα showed the same histological, microbial and immune features of untreated colitic mice. "No DSS + anti-TNFα" group showed a lymphomononuclear infiltrate both at 5th and 12th d at hematoxylin and eosin staining, an increase of in Th1 and Th17 frequency at day 12, an increase of Enterococcaceae at day 5, a decrease of Bacteroides and Clostridiaceae at day 12.

CONCLUSION

Anti-TNFα treatment in experimental model of colitis improves disease activity but it is associated to an increase in Th17 pathway together with gut microbiota alteration.

Authors+Show Affiliations

Istituto di Patologia Speciale Medica, Università Cattolica del Sacro Cuore, Roma 00168, Italy.UOC di Medicina Interna e Gastroenterologia, Area di Gastroenterologia e Oncologia Medica, Dipartimento di Scienze Gastroenterologiche, Endocrino-Metaboliche e Nefro-Urologiche, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Roma 00168, Italy.Istituto di Patologia Speciale Medica, Università Cattolica del Sacro Cuore, Rome 00168, Italy.Dipartimento delle Scienze della Salute della Donna e del Bambino, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Roma 00168, Italy.Istituto di Clinica Ostetrica e Ginecologica, Università Cattolica del Sacro Cuore, Roma 00168, Italy.U.O.S.A. Gineco-Patologia e Patologia Mammaria, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Roma 00168, Italy.Dipartimento di Anatomia Patologica e Istologia, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Roma 00168, Italy.Dipartimento di Microbiologia, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Roma 00168, Italy.Unità di Microbioma Umano, Ospedale Pediatrico Bambino Gesù IRCCS, Roma 00146, Italy.Unità di Microbioma Umano, Ospedale Pediatrico Bambino Gesù IRCCS, Roma 00146, Italy.Unità di Microbioma Umano, Ospedale Pediatrico Bambino Gesù IRCCS, Roma 00146, Italy.Dipartimento di Microbiologia, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Roma 00168, Italy.Dipartimento di Microbiologia, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Roma 00168, Italy.Istituto di Patologia Generale, Università Cattolica del Sacro Cuore, Roma 00168, Italy.Istituto di Patologia Speciale Medica, Università Cattolica del Sacro Cuore, Roma 00168, Italy.Istituto di Patologia Speciale Medica, Università Cattolica del Sacro Cuore, Roma 00168, Italy.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

30948910

Citation

Petito, Valentina, et al. "Anti-tumor Necrosis Factor Α Therapy Associates to Type 17 Helper T Lymphocytes Immunological Shift and Significant Microbial Changes in Dextran Sodium Sulphate Colitis." World Journal of Gastroenterology, vol. 25, no. 12, 2019, pp. 1465-1477.
Petito V, Graziani C, Lopetuso LR, et al. Anti-tumor necrosis factor α therapy associates to type 17 helper T lymphocytes immunological shift and significant microbial changes in dextran sodium sulphate colitis. World J Gastroenterol. 2019;25(12):1465-1477.
Petito, V., Graziani, C., Lopetuso, L. R., Fossati, M., Battaglia, A., Arena, V., Scannone, D., Quaranta, G., Quagliariello, A., Del Chierico, F., Putignani, L., Masucci, L., Sanguinetti, M., Sgambato, A., Gasbarrini, A., & Scaldaferri, F. (2019). Anti-tumor necrosis factor α therapy associates to type 17 helper T lymphocytes immunological shift and significant microbial changes in dextran sodium sulphate colitis. World Journal of Gastroenterology, 25(12), 1465-1477. https://doi.org/10.3748/wjg.v25.i12.1465
Petito V, et al. Anti-tumor Necrosis Factor Α Therapy Associates to Type 17 Helper T Lymphocytes Immunological Shift and Significant Microbial Changes in Dextran Sodium Sulphate Colitis. World J Gastroenterol. 2019 Mar 28;25(12):1465-1477. PubMed PMID: 30948910.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Anti-tumor necrosis factor α therapy associates to type 17 helper T lymphocytes immunological shift and significant microbial changes in dextran sodium sulphate colitis. AU - Petito,Valentina, AU - Graziani,Cristina, AU - Lopetuso,Loris R, AU - Fossati,Marco, AU - Battaglia,Alessandra, AU - Arena,Vincenzo, AU - Scannone,Domenico, AU - Quaranta,Gianluca, AU - Quagliariello,Andrea, AU - Del Chierico,Federica, AU - Putignani,Lorenza, AU - Masucci,Luca, AU - Sanguinetti,Maurizio, AU - Sgambato,Alessandro, AU - Gasbarrini,Antonio, AU - Scaldaferri,Franco, PY - 2018/11/14/received PY - 2019/02/15/revised PY - 2019/02/22/accepted PY - 2019/4/6/entrez PY - 2019/4/6/pubmed PY - 2019/6/25/medline KW - Dextran sodium sulphate colitis KW - Gut microbiota KW - Immune system KW - Mesenchymal lymphnode KW - T cells KW - Tumor necrosis factor α SP - 1465 EP - 1477 JF - World journal of gastroenterology JO - World J. Gastroenterol. VL - 25 IS - 12 N2 - BACKGROUND: Anti-tumor necrosis factor α (TNFα) represents the best therapeutic option to induce mucosal healing and clinical remission in patients with moderate-severe ulcerative colitis. On the other side gut microbiota plays a crucial role in pathogenesis of ulcerative colitis but few information exists on how microbiota changes following anti-TNFα therapy and on microbiota role in mucosal healing. AIM: To elucidate whether gut microbiota and immune system changes appear following anti TNFα therapy during dextran sulfate sodium (DSS) colitis. METHODS: Eighty C57BL/6 mice were divided into four groups: "No DSS", "No DSS + anti-TNFα", "DSS" and "DSS + anti-TNFα". "DSS" and "DSS + anti-TNFα" were treated for 5 d with 3% DSS. At day 3, mice whithin "No DSS+anti-TNFα" and "DSS+anti-TNFα" group received 5 mg/kg of an anti-TNFα agent. Forty mice were sacrificed at day 5, forty at day 12, after one week of recovery post DSS. The severity of colitis was assessed by a clinical score (Disease Activity Index), colon length and histology. Bacteria such as Bacteroides, Clostridiaceae, Enterococcaceae and Fecalibacterium prausnitzii (F. prausnitzii) were evaluated by quantitative PCR. Type 1 helper T lymphocytes (Th1), type 17 helper T lymphocytes (Th17) and CD4+ regulatory T lymphocytes (Treg) distributions in the mesenteric lymph node (MLN) were studied by flow cytometry. RESULTS: Bacteria associated with a healthy state (i.e., such as Bacteroides, Clostridiaceae and F. prausnitzii) decreased during colitis and increased in course of anti-TNFα treatment. Conversely, microorganisms belonging to Enterococcaceae genera, which are linked to inflammatory processes, showed an opposite trend. Furthermore, in colitic mice treated with anti-TNFα microbial changes were associated with an initial increase (day 5 of the colitis) in Treg cells and a consequent decrease (day 12 post DSS) in Th1 and Th17 frequency cells. Healthy mice treated with anti-TNFα showed the same histological, microbial and immune features of untreated colitic mice. "No DSS + anti-TNFα" group showed a lymphomononuclear infiltrate both at 5th and 12th d at hematoxylin and eosin staining, an increase of in Th1 and Th17 frequency at day 12, an increase of Enterococcaceae at day 5, a decrease of Bacteroides and Clostridiaceae at day 12. CONCLUSION: Anti-TNFα treatment in experimental model of colitis improves disease activity but it is associated to an increase in Th17 pathway together with gut microbiota alteration. SN - 2219-2840 UR - https://www.unboundmedicine.com/medline/citation/30948910/Anti_tumor_necrosis_factor_α_therapy_associates_to_type_17_helper_T_lymphocytes_immunological_shift_and_significant_microbial_changes_in_dextran_sodium_sulphate_colitis_ L2 - http://www.wjgnet.com/1007-9327/full/v25/i12/1465.htm DB - PRIME DP - Unbound Medicine ER -