Study shows that even after a change to a healthy diet, the body’s defenses
remain hyperactive

Date:

January 11, 2018

Source:

University of Bonn

Summary:

The
immune system reacts similarly to a high fat and high calorie diet as to a
bacterial infection. Unhealthy food seems to make the body’s defenses more
aggressive in the long term. Even long after switching to a healthy diet,
inflammation towards innate immune stimulation is more pronounced. These
changes may be involved in the development of arteriosclerosis and diabetes.

The immune system reacts
similarly to a high fat and high calorie diet as to a bacterial infection. This
is shown by a recent study led by the University of Bonn. Particularly
disturbing: Unhealthy food seems to make the body’s defenses more aggressive in
the long term. Even long after switching to a healthy diet, inflammation
towards innate immune stimulation is more pronounced. These long-term changes
may be involved in the development of arteriosclerosis and diabetes, diseases
linked to Western diet consumption. The results will be published in the
journal Cell.

The scientists placed
mice for a month on a so-called “Western diet”: high in fat, high in
sugar, and low in fiber. The animals consequently developed a strong
inflammatory response throughout the body, almost like after infection with
dangerous bacteria. “The unhealthy diet led to an unexpected increase in
the number of certain immune cells in the blood of the mice, especially
granulocytes and monocytes. This was an indication for an involvement of immune
cell progenitors in the bone marrow,” Anette Christ, postdoctoral fellow
in the Institute of Innate Immunity of the University of Bonn explains. To
better understand these unexpected findings, bone marrow progenitors for major
immune cell types were isolated from mice fed a Western diet or healthy control
diet and a systematic analysis of their function and activation state was
performed.

“Genomic studies
did, in fact, show that the Western diet had activated a large number of genes
in the progenitor cells. The genes affected included those responsible for
proliferation and maturation,” explains Prof. Dr. Joachim Schultze from
the Life & Medical Sciences Institute (LIMES) at the University of Bonn and
the German Center for Neurodegenerative Diseases (DZNE). Fast food thus causes
the body to quickly recruit a huge and powerful army. When the researchers
offered the rodents their typical cereal diet for another four weeks, the acute
inflammation disappeared. What did not disappear was the genetic reprogramming
of the immune cells and their precursors: Even after these four weeks, many of
the genes that had been switched on during the fast food phase were still
active.

“Fast food
sensor” in the immune cells

“It has only
recently been discovered that the innate immune system has a form of
memory,” explains Prof. Dr. Eicke Latz, Director of the Institute for
Innate Immunity of the University of Bonn and scientist at the DZNE.
“After an infection, the body’s defenses remain in a kind of alarm state,
so that they can respond more quickly to a new attack.” Experts call this
“innate immune training.” In the mice, this process was not triggered
by a bacterium, but by an unhealthy diet.

The scientists were
further able to identify the responsible “fast food sensor” in immune
cells. They examined blood cells from 120 subjects. In some of the subjects,
the innate immune system showed a particularly strong training effect. In these
subjects, the researchers found genetic evidence of the involvement of a
so-called inflammasome. Inflammasomes are key intracellular signaling complexes
that recognize infectious agents and other harmful substances and subsequently
release highly inflammatory messengers. How exactly the NLRP3 inflammasome
recognizes the exposure of the body to Western type diets remains to be
determined.

Interestingly, in
addition to the acute inflammatory response, this also has long-term
consequences for the immune system’s responses: The activation by Western diet
changes the way in which the genetic information is packaged. The genetic
material is stored in the DNA and each cell contains several DNA strands, which
together are about two meters long. However, they are typically wrapped around
certain proteins in the nucleus and thus many genes in the DNA cannot be read
as they are simply too inaccessible.

Unhealthy eating causes
some of these normally hidden pieces of DNA to unwind, similar to a loop
hanging out of a ball of wool. This area of the genetic material can then be
read much easier as long as this temporary unwrapping remains active.
Scientists call these phenomena epigenetic changes. “The inflammasome
triggers such epigenetic changes,” explains Dr. Latz. “The immune
system consequently reacts even to small stimuli with stronger inflammatory
responses.”

Dramatic consequences for
health

These inflammatory
responses can in turn accelerate the development of vascular diseases or type 2
diabetes. In arteriosclerosis for example, the typical vascular deposits, the
plaques, consist largely of lipids and immune cells. The inflammatory reaction
contributes directly to their growth, because newly activated immune cells
constantly migrate into the altered vessel walls. When the plaques grow too
large, they can burst, leading to blood clotting and are carried away by the
bloodstream and can clog vessels. Possible consequences: Stroke or heart
attack.

Wrong nutrition can thus
have dramatic consequences. In recent centuries, average life expectancy has
steadily increased in Western countries. This trend is currently being broken
for the first time: Individuals born today will live on average shorter lives
than their parents. Unhealthy diets and too little exercise likely play a
decisive role in this.

“These findings
therefore have important societal relevance,” explains Latz. “The
foundations of a healthy diet need to become a much more prominent part of
education than they are at present. Only in this way can we immunize children
at an early stage against the temptations of the food industry. Children have a
choice of what they eat every day. We should enable them to make conscious
decisions regarding their dietary habits.”

The research involved
groups from the Netherlands, the USA, Norway and Germany. Latz and Schultze are
members of the excellence cluster “ImmunoSensation,” which
investigates the innate immune system. Latz is considered a leader in the field
of innate immunity and he has been awarded the Gottfried Wilhelm Leibniz Prize
for his work in December 2017. This is considered one of the most prestigious
science awards in Germany.

Story Source:

Materials
provided by University of
Bonn. Note: Content may be edited for style and length.

Journal Reference:

1.    Anette Christ, Patrick
Günther, Mario A.R. Lauterbach, Peter Duewell, Debjani Biswas, Karin Pelka,
Claus J. Scholz, Marije Oosting, Kristian Haendler, Kevin Baßler, Kathrin Klee,
Jonas Schulte-Schrepping, Thomas Ulas, Simone J.C.F.M. Moorlag, Vinod Kumar,
Min Hi Park, Leo A.B. Joosten, Laszlo A. Groh, Niels P. Riksen, Terje Espevik,
Andreas Schlitzer, Yang Li, Michael L. Fitzgerald, Mihai G. Netea, Joachim L.
Schultze, Eicke Latz. Western Diet Triggers NLRP3-Dependent Innate Immune
Reprogramming. Cell, 2018; 172 (1-2): 162 DOI: 10.1016/j.cell.2017.12.013

University
of Bonn. “Fast food makes the immune system more aggressive in the long
term: Study shows that even after a change to a healthy diet, the body’s
defenses remain hyperactive.” ScienceDaily. ScienceDaily, 11 January 2018.
<www.sciencedaily.com/releases/2018/01/180111141637.htm>.