2022
Restoring the
balance
A LITERATURE THESIS ON THE DISBALANCE OF THE GUT
MICROBIOME IN IBD PATIENTS, THE POSITIVE AND NEGATIVE
EFFECTS OF FOOD (PRODUCTION) ON THE BALANCE, AND HOW TO
RESTORE IT.
D.M. MÖHLMANN
VU UNIVERSITY AMSTERDAM
SUPERVISOR DR. A.A. TE VELDE
TYTGAT INSTITUTE FOR LIVER AND INTESTINAL RESEARCH, AMSTERDAM UMC
MSC. BIOMEDICAL SCIENCES
RESEARCH SPECIALISATION IMMUNOLOGY
LITERATURE THESIS (AM_471135)
9 EC
14-03-2022
,Table of contents
Abstract..................................................................................................................................................2
Abbreviations.........................................................................................................................................3
Introduction............................................................................................................................................4
Study Design.......................................................................................................................................7
1. Currently known effects of food.........................................................................................................8
2. The positive and negative effects on the balance.............................................................................10
2.1 Negative effects on the balance.................................................................................................10
2.2 Positive effects on the balance...................................................................................................13
3. Discussion.........................................................................................................................................18
3.1 How do we restore the balance?................................................................................................18
Acknowledgments................................................................................................................................21
References............................................................................................................................................22
1
,Abstract
In inflammatory bowel disease, there is a dysbiosis of the gut microbiome and therefore immune
dysregulation, which result in inflammation and ulceration of the gastrointestinal tract. This
highlights the importance of the gut microbiome-host symbiosis, which has been reported before.
Next to the microbiome, the diet is also important for patients with IBD. Previous studies have
reported compounds of fruits and vegetables, so called phytochemicals, that can have anti-
inflammatory and antioxidative effects. The amount of these compounds in plants seems to be
related to the microbial richness of the soil. In this literature thesis, we look at the balance between
the microbiome of humans, plants, and soil. Also, we will look at the negative effects of food
production on this balance, such as the reduced microbial richness of both soil and plants caused by
modern agricultural practices like the use of pesticides and tillage. Furthermore, we will also look at
the positive effects of phytochemicals, also called plant secondary compounds, that are produced in
plants and can have anti-inflammatory effects on human health. Finally, we will suggest how to
restore this balance, with regenerative agriculture and a phytochemically rich, non-processed food
including diet, which possibly can improve all human health and reduce the onset of chronic Western
diseases, like IBD, in the future.
2
, Abbreviations
ApoE apolipoprotein E
CD Crohn’s disease
COX-2 cyclo-oxygenase 2
CRP C-reactive protein
EC endothelial cells
ERGO ergothioneine
H2O2 hydrogen peroxide
IBD inflammatory bowel disease
ICAM-1 intercellular adhesion molecule 1
IFNƴ interferon gamma
IKK IkappaB kinase
IL interleukin
iNOS inducible nitric oxide synthase
JNK c-Jun N-terminal kinase
LPS lipopolysaccharides
MAPK mitogen-activated protein kinase
NF-ƙB nuclear factor kappa-light-chain-enhancer of activated B cells
NO nitric oxide
PPC plant primary compound
PSC plant secondary compound
RNS reactive nitrogen species
ROS reactive oxygen species
SPM specialized pro-resolving mediators
Th T-helper cells
TLR Toll-like receptor
TNF-α tumor necrosis factor-alpha
UC ulcerative colitis
VCAM-1 vascular cell adhesion molecule 1
3
Restoring the
balance
A LITERATURE THESIS ON THE DISBALANCE OF THE GUT
MICROBIOME IN IBD PATIENTS, THE POSITIVE AND NEGATIVE
EFFECTS OF FOOD (PRODUCTION) ON THE BALANCE, AND HOW TO
RESTORE IT.
D.M. MÖHLMANN
VU UNIVERSITY AMSTERDAM
SUPERVISOR DR. A.A. TE VELDE
TYTGAT INSTITUTE FOR LIVER AND INTESTINAL RESEARCH, AMSTERDAM UMC
MSC. BIOMEDICAL SCIENCES
RESEARCH SPECIALISATION IMMUNOLOGY
LITERATURE THESIS (AM_471135)
9 EC
14-03-2022
,Table of contents
Abstract..................................................................................................................................................2
Abbreviations.........................................................................................................................................3
Introduction............................................................................................................................................4
Study Design.......................................................................................................................................7
1. Currently known effects of food.........................................................................................................8
2. The positive and negative effects on the balance.............................................................................10
2.1 Negative effects on the balance.................................................................................................10
2.2 Positive effects on the balance...................................................................................................13
3. Discussion.........................................................................................................................................18
3.1 How do we restore the balance?................................................................................................18
Acknowledgments................................................................................................................................21
References............................................................................................................................................22
1
,Abstract
In inflammatory bowel disease, there is a dysbiosis of the gut microbiome and therefore immune
dysregulation, which result in inflammation and ulceration of the gastrointestinal tract. This
highlights the importance of the gut microbiome-host symbiosis, which has been reported before.
Next to the microbiome, the diet is also important for patients with IBD. Previous studies have
reported compounds of fruits and vegetables, so called phytochemicals, that can have anti-
inflammatory and antioxidative effects. The amount of these compounds in plants seems to be
related to the microbial richness of the soil. In this literature thesis, we look at the balance between
the microbiome of humans, plants, and soil. Also, we will look at the negative effects of food
production on this balance, such as the reduced microbial richness of both soil and plants caused by
modern agricultural practices like the use of pesticides and tillage. Furthermore, we will also look at
the positive effects of phytochemicals, also called plant secondary compounds, that are produced in
plants and can have anti-inflammatory effects on human health. Finally, we will suggest how to
restore this balance, with regenerative agriculture and a phytochemically rich, non-processed food
including diet, which possibly can improve all human health and reduce the onset of chronic Western
diseases, like IBD, in the future.
2
, Abbreviations
ApoE apolipoprotein E
CD Crohn’s disease
COX-2 cyclo-oxygenase 2
CRP C-reactive protein
EC endothelial cells
ERGO ergothioneine
H2O2 hydrogen peroxide
IBD inflammatory bowel disease
ICAM-1 intercellular adhesion molecule 1
IFNƴ interferon gamma
IKK IkappaB kinase
IL interleukin
iNOS inducible nitric oxide synthase
JNK c-Jun N-terminal kinase
LPS lipopolysaccharides
MAPK mitogen-activated protein kinase
NF-ƙB nuclear factor kappa-light-chain-enhancer of activated B cells
NO nitric oxide
PPC plant primary compound
PSC plant secondary compound
RNS reactive nitrogen species
ROS reactive oxygen species
SPM specialized pro-resolving mediators
Th T-helper cells
TLR Toll-like receptor
TNF-α tumor necrosis factor-alpha
UC ulcerative colitis
VCAM-1 vascular cell adhesion molecule 1
3
