PMID- 30948910
OWN - NLM
STAT- MEDLINE
DCOM- 20190624
LR  - 20200225
IS  - 2219-2840 (Electronic)
IS  - 1007-9327 (Print)
IS  - 1007-9327 (Linking)
VI  - 25
IP  - 12
DP  - 2019 Mar 28
TI  - Anti-tumor necrosis factor alpha therapy associates to type 17 helper T lymphocytes 
      immunological shift and significant microbial changes in dextran sodium sulphate 
      colitis.
PG  - 1465-1477
LID - 10.3748/wjg.v25.i12.1465 [doi]
AB  - BACKGROUND: Anti-tumor necrosis factor alpha (TNFalpha) 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-TNFalpha therapy and on microbiota role in 
      mucosal healing. AIM: To elucidate whether gut microbiota and immune system 
      changes appear following anti TNFalpha therapy during dextran sulfate sodium (DSS) 
      colitis. METHODS: Eighty C57BL/6 mice were divided into four groups: "No DSS", 
      "No DSS + anti-TNFalpha", "DSS" and "DSS + anti-TNFalpha". "DSS" and "DSS + anti-TNFalpha" 
      were treated for 5 d with 3% DSS. At day 3, mice whithin "No DSS+anti-TNFalpha" and 
      "DSS+anti-TNFalpha" group received 5 mg/kg of an anti-TNFalpha 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-TNFalpha 
      treatment. Conversely, microorganisms belonging to Enterococcaceae genera, which 
      are linked to inflammatory processes, showed an opposite trend. Furthermore, in 
      colitic mice treated with anti-TNFalpha 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-TNFalpha showed the same histological, microbial and immune features of 
      untreated colitic mice. "No DSS + anti-TNFalpha" group showed a lymphomononuclear 
      infiltrate both at 5(th) and 12(th) 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-TNFalpha treatment in experimental model of colitis improves disease activity 
      but it is associated to an increase in Th17 pathway together with gut microbiota 
      alteration.
FAU - Petito, Valentina
AU  - Petito V
AD  - Istituto di Patologia Speciale Medica, Universita Cattolica del Sacro Cuore, Roma 
      00168, Italy.
FAU - Graziani, Cristina
AU  - Graziani C
AD  - 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.
FAU - Lopetuso, Loris R
AU  - Lopetuso LR
AD  - Istituto di Patologia Speciale Medica, Universita Cattolica del Sacro Cuore, Rome 
      00168, Italy.
FAU - Fossati, Marco
AU  - Fossati M
AD  - Dipartimento delle Scienze della Salute della Donna e del Bambino, Fondazione 
      Policlinico Universitario "A. Gemelli" IRCCS, Roma 00168, Italy.
FAU - Battaglia, Alessandra
AU  - Battaglia A
AD  - Istituto di Clinica Ostetrica e Ginecologica, Universita Cattolica del Sacro 
      Cuore, Roma 00168, Italy.
FAU - Arena, Vincenzo
AU  - Arena V
AD  - U.O.S.A. Gineco-Patologia e Patologia Mammaria, Fondazione Policlinico 
      Universitario "A. Gemelli" IRCCS, Roma 00168, Italy.
FAU - Scannone, Domenico
AU  - Scannone D
AD  - Dipartimento di Anatomia Patologica e Istologia, Fondazione Policlinico 
      Universitario "A. Gemelli" IRCCS, Roma 00168, Italy.
FAU - Quaranta, Gianluca
AU  - Quaranta G
AD  - Dipartimento di Microbiologia, Fondazione Policlinico Universitario "A. Gemelli" 
      IRCCS, Roma 00168, Italy.
FAU - Quagliariello, Andrea
AU  - Quagliariello A
AD  - Unita di Microbioma Umano, Ospedale Pediatrico Bambino Gesu IRCCS, Roma 00146, 
      Italy.
FAU - Del Chierico, Federica
AU  - Del Chierico F
AD  - Unita di Microbioma Umano, Ospedale Pediatrico Bambino Gesu IRCCS, Roma 00146, 
      Italy.
FAU - Putignani, Lorenza
AU  - Putignani L
AD  - Unita di Microbioma Umano, Ospedale Pediatrico Bambino Gesu IRCCS, Roma 00146, 
      Italy.
FAU - Masucci, Luca
AU  - Masucci L
AD  - Dipartimento di Microbiologia, Fondazione Policlinico Universitario "A. Gemelli" 
      IRCCS, Roma 00168, Italy.
FAU - Sanguinetti, Maurizio
AU  - Sanguinetti M
AD  - Dipartimento di Microbiologia, Fondazione Policlinico Universitario "A. Gemelli" 
      IRCCS, Roma 00168, Italy.
FAU - Sgambato, Alessandro
AU  - Sgambato A
AD  - Istituto di Patologia Generale, Universita Cattolica del Sacro Cuore, Roma 00168, 
      Italy.
FAU - Gasbarrini, Antonio
AU  - Gasbarrini A
AD  - Istituto di Patologia Speciale Medica, Universita Cattolica del Sacro Cuore, Roma 
      00168, Italy.
FAU - Scaldaferri, Franco
AU  - Scaldaferri F
AD  - Istituto di Patologia Speciale Medica, Universita Cattolica del Sacro Cuore, Roma 
      00168, Italy.
LA  - eng
PT  - Journal Article
PL  - United States
TA  - World J Gastroenterol
JT  - World journal of gastroenterology
JID - 100883448
RN  - 0 (Gastrointestinal Agents)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 9042-14-2 (Dextran Sulfate)
RN  - B72HH48FLU (Infliximab)
SB  - IM
MH  - Animals
MH  - Bacteria/drug effects/immunology/isolation & purification
MH  - Colitis, Ulcerative/chemically induced/diagnosis/*drug therapy/immunology
MH  - Colon/drug effects/immunology/microbiology
MH  - Dextran Sulfate/toxicity
MH  - Disease Models, Animal
MH  - Gastrointestinal Agents/*adverse effects
MH  - Gastrointestinal Microbiome/*drug effects/immunology
MH  - Humans
MH  - Infliximab/adverse effects
MH  - Intestinal Mucosa/drug effects/immunology/microbiology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Severity of Illness Index
MH  - Th17 Cells/*drug effects/immunology
MH  - Tumor Necrosis Factor-alpha/*antagonists & inhibitors/immunology
PMC - PMC6441917
OTO - NOTNLM
OT  - Dextran sodium sulphate colitis
OT  - Gut microbiota
OT  - Immune system
OT  - Mesenchymal lymphnode
OT  - T cells
OT  - Tumor necrosis factor alpha
COIS- Conflict-of-interest statement: Authors disclose no any conflict of interest.
EDAT- 2019/04/06 06:00
MHDA- 2019/06/25 06:00
PMCR- 2019/03/28
CRDT- 2019/04/06 06:00
PHST- 2018/11/14 00:00 [received]
PHST- 2019/02/15 00:00 [revised]
PHST- 2019/02/22 00:00 [accepted]
PHST- 2019/04/06 06:00 [entrez]
PHST- 2019/04/06 06:00 [pubmed]
PHST- 2019/06/25 06:00 [medline]
PHST- 2019/03/28 00:00 [pmc-release]
AID - 10.3748/wjg.v25.i12.1465 [doi]
PST - ppublish
SO  - World J Gastroenterol. 2019 Mar 28;25(12):1465-1477. doi: 
      10.3748/wjg.v25.i12.1465.