Curriculum Vitae

• Nama : dr. Luciana Sophie Mariana Rotty, SpPD, FINASIM

• Jabatan : Staf KSM Penyakit Dalam
Divisi Gastroentero-Hepatologi FK UNSRAT
• Tempat/Tanggal lahir : Manado, 5 April 1971
• Riwayat Pendidikan. : S1. : FK UNSRAT
SP-1 : FK UNSRAT
• Organisasi : IDI Manado
PEGI, PGI, PPHI
 MICROBIOME
IN
INFLAMMATORY BOWEL
DISEASE

Gastroenterology and Hepatology Division

Department of Internal Medicine
Faculty of Medicine Sam Ratulangi University/
RSUP Prof.dr.R.D.Kandou Manado
 INTRODUCTION
We are living with a tremendous amount of microorganisms in our guts,
ranging from bacteria, archaea to virus and fungi.

The microbiome has received increasing attention over the last 15 years.

The gut microbiota is now considered an important partner of human cells,

interacting with virtually all human cells.

IBD has been associated with dysbiosis

 Microbiota composition and IBD

Multiple studies have documented differences in the composition of the gut microbiota
between patients with IBD and healthy individuals.

The phylum Firmicutes — specifically Faecailbacterium prausnitzii — is often reduced in

proportional abundance in the stool of patients with Crohn's disease.

Members of the Proteobacteria phylum, such as Enterobacteriaceae, including Escherichia

coli, are commonly increased in patients with IBD relative to healthy individuals.

Dysbiosis is primarily associated with disease state rather than environmental or genetic
factors.

Ni J, Wu GD, Albenberg L, Tomov VT. Gut microbiota and IBD: causation or correlation?
Nat Rev Gastroenterol Hepatol. 2017 October ; 14(10): 573–584.
 DEFINITIONS
Microbiota Microbiome Metabolome Metagenome
Collection of all Refer to the genes Refers to the Refers to the entire
taxa constituting harboured by quantitative genetic material
microbial microbes. complement of all present in a sample.
communities : Currently, the term the low Composed of the
bacteria, archeae, ‘microbiome’ is also molecular-weight genomes of several
fungi, protists. commonly used to molecules present individual organisms
refer to the in a biological
microorganisms sample
themselves (ie, the Refers to the entire viral genetic
microbiota) Virome material present in a sample.
Consists of the genomes of
Cani PD. Human gut microbiome: hopes, threats and viruses
promises. Gut 2018;67:1716–1725
 Technologies to investigate the gut microbiota

Durack J, Lynch SV. The gut microbiome: Relationships with disease and opportunities for therapy. J Exp Med 2019:216;6.
.
 INFLAMMATORY
BOWEL DISEASE

FamilyDoctor.org
 Idiopathic

Inflammation Chronic

IBD
Gastrointestinal
Relapsing
tract

Immune
activation

Sands BE, Siegel CA. Crohn’s disease. In: Feldman M, Friedman L, Brandt L, eds. Sleisenger and Fordtrans’s
Gastrointestinal and Liver Disease, 10th Ed. Philadelphia: Elsevier and Saunders 2016. Chapter 115
John Hopkins Medicine. Crohn’s disease. Maryland:2013
Dar MJ, Ali H, Khan A, Khan GM. Polymer-based drug delivery: the quest for local targeting of inflamed
intestinal mucosa. J of DrugTargeting 2017.
 EPIDEMIOLOGY OF IBD

Friedman S, Blumberg RS. Inflammatory bowel disease. In: Longo DL, Fauci AS, et al,eds. Harrison’s gastroenterology and
hepatology 10th ed. New York: Mc Graw Hill 2010. Chapter 16.
 The Global Distribution of Inflammatory Bowel Disease

Molodecky, Natalie A., et al. "Increasing incidence and prevalence of the inflammatory bowel diseases with time, based on
systematic review."Gastroenterology 142.1 (2012): 46-54.
Anatomic Distribution of Crohn’s Disease and Ulcerative Colitis.

John Hopkins Medicine. Crohn’s disease. Maryland:2013

Endoscopic appereance of Chron’s disease
A. Typical aphthous ulcers (arrows), consisting of a
central white depression surrounded by a
slightly elevated, erythematous rim only a few
millimeters in diameter.
B. Findings more typical of advanced disease, with
erythema, edema, and a cobblestoned
appearance.
C. Stellate ulcers (arrows) in the terminal ileum.
D. Discrete ulcers (arrows) with normal
intervening mucosa, typical of the patchy
inflammation seen in Crohn’s disease.

Sands BE, Siegel CA. Crohn’s disease. In: Feldman M,

Friedman L, Brandt L, eds. Sleisenger and Fordtans’s
Gastrointestinal and Liver Disease, 10th Ed. Philadelphia:
Elsevier and Saunders 2016. Chapter 115
 Colonoscopic findings of Ulcerative Colitis
Spectrum of severity of UC

A. Mild UC demonstrating edema, loss of vascularity, and patchy subepithelial

hemorrhage.
B. Severe UC demonstrating loss of vascularity, hemorrhage, and mucopus. The
mucosa is friable, with spontaneous bleeding as well as bleeding after the
mucosa is touched by the endoscope.
C. Colonoscopy findings in a patient with chronic UC undergoing surveillance for
colorectal cancer. The ascending colon (top left), transverse colon (top right),
and descending colon (bottom left) are normal, but the sigmoid colon shows
active inflammation (bottom right). F, A biopsy specimen of the normal-
appearing colon demonstrates abnormal archi- tecture with shortened crypts Osterman MT, Lichtenstein GR. Ulcerative Colitis. SLEISENGER AND
but no active colitis.
FORDTRAN’S GASTROINTESTINAL AND LIVER DISEASE, 10TH EDITION
Philadelphia: Elsevier and Saunders 2016. Chapter 116
 Extraintestinal Manifestations
of Crohn’s Disease

John Hopkins Medicine. Crohn’s disease.

Maryland:2013
Tabel. Differential
diagnosis of Ulcerative
Colitis and Crohn’s
Disease

Boumgart DC, Sandborn WJ. Inflammatory

bowel disease: clinical aspects and
established and evolving therapies. Lancet
2007
 TREATMENT OF IBD

McDermott RP (2014): Management of mild to moderate ulcerative colitis. In: UpToDate, Basow, DS (Ed), Waltham, MA. Cited
11/24/15.
 THE ROLE OF GUT MICROBIOME
IN
INFLAMMATORY BOWEL DISEASE

Forbes.com
Old Paradigm of Contributing Factors
of IBD
 Role of the gut microbiome, host and environmental factors in the aetiopathogenesis of
inflammatory bowel disease.

Dysbiotic changes in the gut microbiome may be influenced by diet and other environmental factors and predispose to inflammatory bowel
disease (IBD). A small proportion of IBD patients have demonstrable genetic susceptibility factors. NOD2: Nucleotide-binding oligomerization
domain-containing protein 2; ATG16L1: Autophagy related protein 16-like 1; IL-23R: Interleukin 23 receptor.
Hold GL, Smith M, Grange C, et al. Role of the gut microbiota in inflammatory bowel disease pathogenesis: What have we learnt in the past 10 years? World J Gastroenterol 2014
February 7; 20(5): 1192-1210
 The dominant gut microbial phyla

Firmicutes

Bacteroidetes

Actinobacteria

Proteobacteria

Fusobacteria

Verrucomicrobia

The dominant gut microbial phyla are Firmicutes, Bacteroidetes, Actinobacteria, Proteobacteria, Fusobacteria, and
Verrucomicrobia, with the two phyla Firmicutes and Bacteroidetes representing 90% of gut microbiota.
Rinninella E, Raoul P, Cintoni M, et al. What is the Healthy Gut Microbiota Composition? A Changing Ecosystem across Age, Environment, Diet,
and Diseases. Microorganisms J 2019;7,:14.
 Physiological
role of the gut
microbiota

Nishida A, Inoue R, Osamu Inatomi, et al. Gut microbiota in the pathogenesis of inflammatory bowel disease. Clinical Journal of Gastroenterology
(2018) 11:1–10
 DYSBIOSIS IN IBD

Harris KG, Chang EB. The intestinal microbiota in the pathogenesis of inflammatory bowel diseases : new insight
into complex diseases. Clinical science 2018:132;18:2013-2028.
 Outcome in host immune system
Dysbiosis in IBD and mucosal integrity

Nishida A, Inoue R, Osamu Inatomi, et al. Gut microbiota in the pathogenesis of inflammatory bowel disease. Clinical Journal of Gastroenterology
(2018) 11:1–10
Microbial
signatures of a
healthy gut
and IBD

SOMMER F, RUHLEMANN MC, BANG C, ET

AL.Microbiomarkers in inflammatory bowel
diseases: caveats come with caviar. Gut 2017;
66:10 .
Interactions between microbiota and host genetic and environmental factors
contribute to the pathogenesis of IBD
Under healthy conditions (left panel), pathogens
are suppressed by beneficial commensal
bacteria through the induction of antimicrobial
proteins, such as IL-10 and REG3γ, thus
maintaining homeostasis. In IBD (right panel), a
combination of genetic factors and
environmental factors (such as stress, diet, and
antibiotic) lead to dysbiosis, which in turn
affects barrier integrity, innate, and adaptive
immunity, resulting in uncontrolled chronic
inflammation and hyper-activation of T helper 1
(Th1) and Th17 cells, increase in tight junction
permeability, reduction in regulatory T (Treg)
cells, and decrease in REG3γ and IL-10. ATG16L,
autophagy-related 16-like; CARD9, caspase
recruitment domain family member 9; FUT2,
fucosyltransferase 2; IBD, inflammatory bowel
disease; IL-10, interleukin 10; IRGM, immunity-
related GTPase M; NOD2, nucleotide-binding
oligomerization domain-containing protein 2;
REG3γ, C-type lectin regenerating islet-derived
protein 3γ.

Zhang M, Sun K, Wu Y. interactions between intestinal

Microbiota and Host immune Response in inflammatory
Bowel Disease. Frontiers in Immunology 2017;8:942 .
 Probiotics Fecal Microbiota Transplantation
• living microorganisms • fecal infusion
• modulating the intestinal microflora • transfer of intestinal bacteria from a
• improve immune system healthy donor to restore the
• preexisting microflora stability intestinal microbiota of a diseased
• inhibit pathogen colonization, individual
• stimulating intestinal epithelial cell • gained interest as a novel therapy
barrier responses option.
• Lactobacillus and Bifidobacterium most • FMT has been reported to reduce
common symptoms in about 20% of IBD
patients
Zhang M, Sun K, Wu Y. interactions between intestinal Microbiota and Host immune Response in inflammatory Bowel Disease. Frontiers
in Immunology 2017;8:942 .
 THANK YOU

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