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Diet, Digestive Health, and Autoimmunity: The Foundations to an Autoimmune Disease Food Pyramid—Part 2

Diet, Digestive Health,
and Autoimmunity:
The Foundations to an Autoimmune
Disease Food PyramidPart 2
Bradley Leech, BHSc, Bradley McEwen, PhD, MHSc, and Eric Owusu Sekyere, PhD, MSc
Diet and dietary components are known to have a direct
impact on the modifiable risk factors for autoimmune dis-
ease. In this study, we review a selection of popular diets—
Mediterranean, vegetarian/vegan, Paleolithic, gluten-free,
and a low arachidonic acid diet—for their effect on digestive
health and autoimmune disease. Clinical trials of these diets
demonstrated that including or excluding particular dietary
components and modeling a diet based on whole food eating
reduces intestinal dysbiosis, supports intestinal integrity, and
modulates inflammation. Dietary strategies, such as limit-
ing arachidonic acid to <90 mg per day, avoiding gluten-
containing products, consuming fiber, incorporating fermented
foods, increasing fruit and vegetable intake to above six por-
tions daily, and moderating sodium and long-chain saturated
fat consumption may improve digestive health. Incorporating
these dietary aspects may lay the foundations for the devel-
opment of an “Autoimmune Disease Food Pyramid” as a
preventive health measure and a public health initiative.
Keywords: autoimmune disease, diet, dysbiosis, micro-
biota, Mediterranean diet
In Part 1 of this article, the influence of diet as the major link
underpinning the known modifiable risk factors for the devel-
opment of digestive health-related autoimmune diseases was
discussed. Part 1 also sketched the direct influence of diet and its
components on gut microbial imbalance or dysbiosis, their ef-
fect on intestinal integrity and loss of control in preventing
microbial and dietary antigens translocation, leading to sys-
temic and intestinal inflammation. Diet and dietary components
are known to have a direct impact either positively or negatively
on the modifiable risk factors for autoimmune disease (Fig. 1).
The aim of Part 2 of this article is to review the complex in-
teractions between diet and digestive health in autoimmune
disease and to propose dietary strategies for the prevention and
management of autoimmune disease. Current popular diets,
including the Mediterranean diet, vegetarian/vegan diet, Pa-
leolithic (paleo) diet, gluten-free diet, and a low arachidonic
acid diet, are reviewed for their effectiveness in supporting di-
gestive health and autoimmune disease. Finally, the concept of
an “Autoimmune Disease Food Pyramid” is introduced.
Mediterranean Diet
The Mediterranean diet is one of the most well-known
and researched diets for its recognized beneficial effects on
The Mediterranean diet contains an abundant amount
of fresh fruit and vegetables, whole grains, legumes, nuts, fish,
monounsaturated fats from olive oil, and moderate red wine
The Mediterranean diet may have the potential
to reduce rheumatoid arthritis (RA) activity, leading to an im-
provement in physical function and vitality.
A Mediterranean-
based diet may also normalize microbiota in Crohn’s disease.
The Mediterranean diet has also been observed to increase the
microbiota’s production of short chain fatty acids (SCFAs),
thereby improving and maintaining the health of the digestive
and intestinal integrity.
The Mediterranean diet shows
promise for a number of health conditions; however, only
limited research was found in the management of autoimmune
disease. The Mediterranean diet appears to support the micro-
biota and reduction in inflammatory markers and oxidative
stress and, therefore, a number of the modifiable risk factors
associated with autoimmune disease (Table 1).
Vegetarian and Vegan Diet
Vegetarian and vegan diets exclude the consumption of
meat, poultry, and fish
; in addition, a vegan diet excludes the
158 DOI: 10.1089/act.2020.29287.ble MARY ANN LIEBERT, INC. VOL. 26 NO. 4
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consumption of any products from animals, such as animal
milk, eggs, and honey.
It appears that these diets have
no limitation on processed grains, refined sugars, omega-6
polyunsaturated fatty acids (PUFAs), or sodium consumption.
However, vegetarian and vegan diets are known to contain
higher intake of fruits and vegetables, antioxidant vitamins,
and minerals,
contributing to their beneficial effects on
Vegetarian diets have shown a decrease in arachidonic acid
concentration in platelets. Increased arachidonic acid con-
centration leads to platelet hyperaggregation, which is im-
plicated in cardiovascular disease (CVD).
One study has
demonstrated that increasing fruit and vegetable intake to
greater than six portions daily reduced C-reactive protein
(CRP) levels (P50.001).
This suggests that vegetarian and
vegan diets potentially have an anti-inflammatory effect.
Both fruit and vegetables, including orange juice,
and tomato juice,
have been shown to
reduce several inflammatory cytokines in human clinical tri-
als. A high protein/low carbohydrate diet (137 g protein, 143 g
fat, and 22 g carbohydrate per day) has been shown to reduce
intestinal butyrate by 50% in a four-week trial of 17 obese
Although this study used extremely low carbohydrate
levels, it does demonstrate the impact that diet can have on
protective factors such as reduced intestinal butyrate. In a hu-
man study, a diet high in animal protein, except fish, increased
CRP levels after four weeks, whereas vegetable protein had no
impact on inflammatory markers.
It is speculated that the
increased inflammation associated with meat consumption may
arise from high levels of long-chain saturated fats.
Saturated fats bind to Toll-like receptor (TLR)4 and activate
nuclear factor-kB gene transcription resulting in proin-
flammatory cytokines such as tumor necrosis factor-aand
interleukin (IL)-6.
Long-chain saturated fats may also
increase intestinal permeability,
resulting in postprandial
This rise in inflammation and increased in-
testinal permeability may further contribute to the develop-
ment of dysbiosis, thereby contributing to the dysregulation
of the immune system.
A semivegetarian diet can also
help to maintain remission in Crohn’s disease.
Long-chain saturated fat consumption over the long term
may lead to dysbiosis and increased lipopolysaccharide-
bearing bacteria species that promote inflammation through
the induction of TLR4.
The amount of fiber and protein
consumption can promote the growth of different species of
bacteria and their metabolite by-products.
Both vegetarian
and vegan diets can alter stool pH through increasing SCFA
production to a level similar to that found in a healthy diges-
tive system. This correction in stool pH additionally prevents
potentially pathogenic bacteria from overgrowing.
A randomized placebo-controlled trial consisting of 53
subjects with RA compared a vegetarian diet with an omniv-
orous diet (control, usual Westernized diet).
After 13 months,
both the levels of CRP (P<0.0001) and pain (P<0.02) de-
creased in the vegetarian group. A change in fecal microbiota
correlated with clinical improvements of RA. In the vegetarian
diet group, concentrations of anti-Proteus mirabilis immuno-
globulin G decreased (P<0.05), alongside a decrease in
clinical features of RA such as duration of morning stiff-
ness (P<0.0001), grip strength (P<0.02), tender joints
Figure 1. The interplay between autoimmune disease, dysbiosis, increased intestinal permeability, immune dysregulation, and inammation.
IL, interleukin; NF-kB, nuclear factor-kappa B; Th, T helper cells.
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Table 1. Clinical Trials and Observational Studies of Diet and Autoimmune Disease
Diet Intervention Length Participants (M/F) Study design Disease Result Reference
Mediterranean diet
vs. Western diet
12 Weeks 51 Subjects with controlled yet
active RA for >2 years
Diet: (M5/F21) mean 58 years
Control: (M5/F20) age 3575 mean 59
parallel feeding
CRP (P50.006)
Swollen joints count
Pain (P50.006)
Physical function and vitality
et al.
based diet
based diet inter-
6 Weeks 8 Subjects with active yet stable
Crohns disease (M2/F6), mean 45.4
years (3160)
Altered gene expression
Microbiota diversity toward
normal range
et al.
Vegetarian diet Vegetarian diet vs.
omnivorous diet
13 Months 53 Subjects with RA
Diet: 27 subjects
Control: 26 subjects
single-blind trial
Reduced pain (P<0.02)
Reduced CRP (P<0.0001)
Reduced anti-Proteus
mirabilis IgG (P<0.05)
Reduced disease activity
SVD (red meat
once every
2 weeks, sh
once a week)
SVD vs. omnivorous
24 Months 22 Subjects in remission at high-
risk for relapse (M14/F8) mean 26.5
years (1977)
Diet: 16
Control: 6
clinical trial
92% Remission maintained
on SVD
25% Remission maintained
on omnivorous diet
et al.
vegan diet
Gluten free vegan
diet vs. nonvegan
12 Months 66 Subjects with active RA
Diet: 38 subjects mean 50.0 years
Control: 28 subjects mean 50.8
parallel feeding
Responders subgroup
CRP (P<0.05)
IgG anti-gliadin
IgG anti-b-lactoglobulin
et al.
Gluten free vs. glu-
ten-containing diet
12 Months 40 Subjects at risk of celiac disease
based on positive endomysia
Diet: (M11/F9) mean 42 years
Control: (M15/F5) mean 42 years
parallel feeding
Mean mucosal villous height
increased (P<0.001)
Indigestion (P50.006)
Reux (P50.05)
et al.
Paleo-based diet,
exercise, medita-
tion, and massage
12 Months 9 Subjects with secondary
progressive MS
(M1/F8) mean 52.4 years (4557)
pilot intervention
MS Reduced fatigue (P<0.05) Bisht
et al.
Low arachidonic
acid diet
(<90 mg daily)
Low arachidonic
acid diet crossover
to Western
diet with placebo
crossover with sh
3 Months each
diet with
2 months
68 Subjects with active RA
8 Subjects removed from data
Diet: (M2/F28) mean 58.0 years
Control: (M2/F28) mean 56.8 years
Low arachidonic acid diet:
Enhanced effect of sh oil
Number of tender or
swollen joints
Pain (P<0.05)
et al.
Sodium intake n/a 24 Months 70 Subjects with relapsing-
remitting MS
(M16/F54) mean 37.5 years
Observational MS High sodium ( >4.8 g)
3.95-fold exacerbation
Clinical features of MS
3.4-fold greater chance of
lesions on MRI
et al.
, increase; , decrease; CRP, C-reactive protein; F, female; IgG, immunoglobulin G; IL, interleukin; M, male; MRI, magnetic resonance imaging; MS, multiple sclerosis; n/a, not applicable; paleo, Paleolithic; RA, rheumatoid arthritis;
SVD, semivegetarian diet.
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(P<0.0001), and swollen joints (P<0.02). P. mirabilis is a
known bacterium capable of triggering RA through molecular
Furthering the importance of a vegetarian diet in
RA, it has been observed that the prevalence of RA increases
alongside the consumption of animal meats and offal fat,
whereas a low-fat vegan diet has been shown to improve
symptoms of RA, including joint tenderness (P<0.01), joint
swelling (P<0.02), and morning stiffness (P<0.04).
In a dietary intervention study,
10 healthy volunteers
consumed either an animal-based (high in long-chain saturated
fats) or plant-based (low in long-chain saturated fats) diet for
five days. The animal-based diet increased the abundance and
activity of Bilophila wadsworthia, a bacterium with the ability
to trigger inflammatory bowel disease.
These results indi-
cated that increased animal-derived long-chain saturated fats
can be a major causative factor of increased B. wadsworthia.
The increased consumption of fruit and vegetables seen in a
vegetarian and vegan diet supports digestive health and may
reduce inflammation. Clinical trials indicate the combined
negative effect that long-chain saturated fats and animal
protein have on altering intestinal microbiota, in addition to
increased intestinal permeability and inflammation. This sug-
gests that reducing the consumption of animal products im-
proves these modifiable risk factors of autoimmune disease.
Gluten-Free Diet
Celiac disease affects 1% of the population worldwide, with
most cases undiagnosed.
This autoimmune disease becomes
apparent when genetically susceptible individuals are ex-
posed to gluten, resulting in autoantibodies, villous atrophy,
and gastrointestinal upset.
Gluten is considered a causative
and/or associated factor of celiac disease, type 1 diabetes, and
autoimmune thyroid disease.
Gluten-containing products
include wheat, rye, and spelt.
Gluten is considered to be proinflammatory,
a contributing
agent in dysbiosis,
intestinal permeability altering,
and a digestive irritant.
Gliadin, a protein
found within gluten, interacts with the intestinal mucosa trig-
gering enterocytes to release IL-8 and arachidonic acid.
a proinflammatory mediator, has been associated with the
alteration of intestinal microbiota resulting in dysbiosis.
Inflammation-induced dysbiosis has a strong correlation with
celiac disease,
Crohn’s disease,
and potentially other au-
toimmune diseases. Gliadin has the ability to increase intes-
tinal permeability through activation or upregulation of the
zonulin pathway.
Zonulin acts upon the tight junctions, in-
creasing intestinal permeability.
Recent research has dem-
onstrated the possibility that the effect of gliadin on intestinal
permeability is experienced by all individuals whether or not
they have celiac disease or are sensitive to gluten.
ever, the degree of intestinal permeability is significantly
greater in celiac disease and gluten-sensitive individuals than
individuals with no known sensitivities to gluten.
intestinal permeability has a strong link with the development
and progression of autoimmune disease. The development
and progression of autoimmune disease may occur through
the molecular mimicry of various antigens, such as dietary,
dysbiotic, or infectious antigens.
Elimination of gluten in celiac disease has been shown to
increase the absorption of iron, vitamin B12, vitamin D, and
folic acid.
A gluten-free diet (removal of gluten-containing
products, e.g., wheat, rye, and spelt) is considered to be the
first line of treatment for celiac disease (removal of the trig-
An Australian study
found that gluten-free products
and gluten-containing products have a similar nutritional
profile, with the only significant difference being gluten-free
products had less protein. A gluten-free vegan diet based
on whole foods may reduce inflammation and RA disease
whereas reducing immunoreactivity to food an-
One study demonstrated that individuals at risk of
celiac disease showed positive outcomes when a gluten-free
diet is followed.
Gluten has the ability to cause inflammation and potentially
dysbiosis, all of which may contribute to autoimmune disease
progression and development. A gluten-free diet can be con-
sidered an anti-inflammatory, immune modulating, and di-
gestive supportive diet. Combining a gluten-free diet with a
whole food diet may support the diversity of microbiota and
provide a beneficial effect on the digestive system and auto-
immune disease.
Paleolithic Diet
The paleo diet promotes the consumption of lean meats,
seafood, fruits, vegetables, nuts, and eggs, whereas restricting
grains (e.g., wheat, rice, and spelt), legumes, dairy, salt, refined
fats, and processed carbohydrates/sugar.
The paleo diet
has growing evidence to support weight loss,
metabolic hormones (incretin),
improved glucose control,
and metabolic syndrome.
In addition, it may be associated
with lower levels of systemic inflammation and oxidative
A paleo-based diet alongside lifestyle changes has
been shown to improve fatigue in multiple sclerosis (MS).
Currently, the paleo diet, despite worldwide popularity, lacks
sufficient research to support the benefits in autoimmune dis-
Nevertheless, research suggests aspects of the paleo
diet support healthy digestion,
reduce intestinal inflamma-
and have immune modulating effects,
all of which
have direct correlationswith autoimmune disease management.
Despite limited clinical trials, the paleo diet has a potential
use in the management of autoimmune disease, given elements
of the inclusion and exclusion of specific dietary components.
The following questions can be asked: Is the paleo diet sup-
portive for autoimmune disease as all triggers are removed? Or
does the paleo diet correct immune dysfunction? These ques-
tions are still left unanswered. However, the dual action of
being gluten-free with the emphasis on whole food eating
enables the paleo diet to address intestinal inflammation and
modulate immunoreactivity.
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Low Arachidonic Acid Diet
Many dietary components are considered pro- or anti-
The major contributors to anti-inflammatory
regulation are the omega-3 PUFAs eicosapentaenoic acid
(EPA) and docosahexaenoic acid (DHA). The other essential
PUFAs responsible for the inflammatory cascade are omega-6
(linoleic acid) and arachidonic acid. These fatty acids form part
of every cell membrane and determine the cytokines released,
either pro- or anti-inflammatory.
Arachidonic acid is proin-
flammatory and found primarily in animal products.
dietary consumption of arachidonic acid is associated with
greater cellular membrane percentage of this proinflammatory
fatty acid. Higher dietary arachidonic acid consumption di-
rectly increases proinflammatory CRP (P 50.039).
though linoleic acid can be converted to arachidonic acid, a
systematic review found no correlation between increased
dietary linoleic acid and tissue arachidonic acid content.
Therefore, arachidonic acid is considered more inflammatory
than linoleic acid. The human physiological requirement of
omega-6:omega-3 ratio is suggested to be 1–4:1.
If this ratio
becomes imbalanced, as seen in the Western diet (16–20:1),
the result is greater arachidonic acid released upon stimula-
tionbymolecularinammatorytriggers. Infection and tissue
injury trigger the innate immune system to indirectly stimu-
late arachidonic acid release as part of the homeostatic
mechanism for tissue repair.
Dietary components such as
gluten can also trigger an abnormal/inappropriate arachidonic
acid release.
A low arachidonic acid diet is considered to be <90 mg of
arachidonic acid consumption per day.
A low arachidonic
acid diet has been shown to be beneficial for the joints of RA
Reducing arachidonic acid may reduce the se-
verity of inflammation and consequently protects the micro-
biota balance from dysbiosis
and intestinal integrity
from the damaging effects of inflammatory prostaglandins
and leukotrienes. The meat consumption of various Wester-
nized countries exceed 90 mg of arachidonic acid daily
(Table 2),
as the approximate daily consumption of meat is
323 g for Americans, 226 g for the British, and 332 g for
Furthermore, the ratio of omega-6:omega-3
can differ greatly depending on the feed that the animals are
fed, for example, grass-fed animals contain higher omega-3,
whereas grain-fed animals contain higher omega-6.
milk on average contains 62% more omega-3 and 25% less
A double-blind crossover study compared two groups: a low
arachidonic acid diet (<90 mg/d) and a Western style diet with
a crossover of fish oil supplement or placebo in 68 subjects
with active RA.
The study ran over a period of nine months,
which included a one month run in period, three months on one
treatment, then a two month washout period before crossing
over to the other treatment for three months. This study dem-
onstrated that a low arachidonic acid diet alone can reduce the
number of swollen or tender joints in RA subjects when
compared with the Western diet, where in contrast the number
of swollen joints increased. There was a significant associa-
tion between arachidonic acid consumption and RA disease
activity (P<0.001). In addition, the low arachidonic acid diet
enhanced the effects of fish oil when compared with the
Western diet.
A low arachidonic acid diet addresses one of the driving
principles of autoimmune disease—the inflammation. Redu-
cing arachidonic acid, through limiting animal product con-
sumption, to <90 mg of arachidonic acid daily, has been shown
to directly modulate the inflammatory cascade, as less sub-
strate (arachidonic acid) is available for eicosanoid synthe-
This subsequently modulates autoimmune disease
progression, such as seen in RA.
Furthermore, reducing
the arachidonic acid content of the previously discussed diets
(Mediterranean diet, vegetarian diet, gluten-free diet, and pa-
leo diet) may provide a diet or combination of diets that could
be potentially used for the prevention and management of
autoimmune disease.
The Effect of Dietary Sodium Intake on the
Immune System
The effect of sodium on blood pressure and CVD has been
well established.
Sodium is more highly concentrated in
lymphoid tissues compared with plasma, indicating its role
in the adaptive immune response.
Sodium can modulate the
immune system and excessive consumption can promote in-
In vitro work on human cells has demon-
strated that moderate to high concentrations of sodium
activates or upregulates production of T helper cells (Th)17
cells, therefore worsening autoimmune disease progression.
Regulatory T (Treg) cells are known to play a central
role in maintaining self-tolerance. It has been demonstrated
Table 2. Arachidonic Acid Content per 100 g
Common items 100 g of edible portion 90 mg of AA
Chicken egg 156 57.7
Turkey (no skin) 120 75.0
Goat shoulder 109 82.6
Lamb loin chop 84 107.1
Chicken (no skin) 80 112.5
Pork (with fat) 80 112.5
Lamb (Australian) 69 130.4
Goat leg 65 138.5
Cows milk 60 150.0
Pork loin (no fat) 60 150.0
Beef rib eye 46 195.7
See Hibbeln et al.
AA, arachidonic acid.
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that increased sodium can inhibit the suppressive capacity of
Treg cells,
affecting self-tolerance. A longitudinal
demonstrated an intake of 12 g of salt (6.5 g sodium)
per day was associated with higher numbers of monocytes,
whereas lower intake of salt, 6 g (2.3 g sodium) per day,
showed reductions in IL-6 and IL-23 (proinflammatory cyto-
kines) and enhanced the production of anti-inflammatory
cytokine IL-10. These three cytokines have a direct link with
autoimmune disease. Particularly, IL-6 and IL-23 are both
involved with Th17 development,
and IL-10 exerts immu-
noregulatory and anti-inflammatory actions.
High sodium
intake has also been associated with more than double the risk
of RA among smokers
and greater clinical features of MS
with increased lesions.
Recently, an animal model study has suggested that the
effects of sodium on the immune system may be gene and sex
Further research is required to determine which
individuals may be at greatest risk of sodium influencing the
immune system. Nevertheless, excessive dietary salt con-
sumption may now be considered a potential risk factor for
autoimmune disease through induction of Th17 cells and
exacerbation of autoimmune disease.
A two-year observational study of 70 relapsing-remitting
MS patients
demonstrated high sodium consumption
(>4.8 g/d) was associated with greater clinical features of
MS and a 3.4-fold increased chance of lesions develop-
MS by 2.75- and 3.95-fold in medium and high sodium
groups, respectively, when compared with the low sodium
A number of studies
suggest a strong association be-
tween high sodium consumption and autoimmune disease.
Currently, there is no set upper limit of sodium intake for
individuals with autoimmune disease. Further research is re-
quired to determine if restrictions on sodium intake are nec-
essary in individuals with autoimmune disease, such as seen
with CVD. Of interest, Americans on average consume
3330 mg of sodium per day (above the daily limit of 2300 mg)
and obtain the greatest percentage of sodium from deli/cured
meats and bread/rolls.
Subsequently, these items of food
are also associated with autoimmune disease given that they
contain gluten,
arachidonic acid,
and long-chain satu-
rated fat.
The Next Step: Formation of an Autoimmune
Disease Food Pyramid?
The diets discussed in this article have shown some form
of positive impact on digestive health or autoimmune dis-
Despite their variation in dietary compo-
nents, such as gluten, long-chain saturated fats, arachidonic
acid, fiber, protein source, and sodium, there are some com-
ponents within each diet that support the microbiota, regulate
the immune system, have anti-inflammatory effects, and im-
prove intestinal integrity. Particularly, some of the shared
components that have a negative impact on autoimmune dis-
eases include gluten, long-chain saturated fats, and arachidonic
acid. Gluten is proinflammatory
and immune modulating,
yet the Mediterranean diet with its anti-inflammatory effects
contains gluten, while still supporting RA.
When comparing
the paleo diet with the vegan/vegetarian diet, both have been
used in relation to autoimmune disease; however, they differ
significantly in their content of long-chain saturated fats and
arachidonic acid.
A theory on autoimmune disease proposes the idea that re-
moval of any one of the key elements (genes, environmental
triggers, or impaired intestinal permeability) would eliminate
autoimmune disease progression.
This theory may explain
how each diet discussed in this article had some form of
positive impact on autoimmune disease, regardless of the di-
etary components. This raises a number of questions: Would
combining the beneficial characteristics and excluding the
detrimental attributes of each diet amount to greater outcomes
in autoimmune disease management? Is combining and ex-
cluding different dietary components a feasible idea for a
public health initiative for individuals with or susceptible to
autoimmune disease? Do the beneficial components of some
diets, for example, Mediterranean diet, mask the effects of
the negative components, such as gluten? Can removing or
reducing the negative components of the diet enhance or im-
prove the effectiveness of the beneficial components of the
diet as a tool for the management of autoimmune disease or
other diseases? This idea of combining different dietary
components and limiting others can be seen in both CVD and
cancer management.
For example, CVD management includes limiting sodium
intake to 1500 mg per day, as sodium can influence blood
pressure (hypertension), a known risk factor for CVD.
American Heart Association also advises that saturated fats
should not exceed 5%–6% of daily energy intake.
In regard
to cancer risk reduction, the World Health Organization
monograph evaluating the consumption of red and processed
meats concluded that each 50 g of processed meat eaten
daily increases the risk of colorectal cancer by 18% .
number of cancer institutions in the United States, United
Kingdom, and Australia advise to limit meat consumption
to no more than three to four small servings of lean meat
weekly in cancer management.
These examples demon-
strate how individuals with or those at risk of a particular
disease may obtain benefit from adhering to specific dietary
A current hypothesis
suggests that modern food addi-
tives (sugars, salt, organic solvents, gluten, emulsifiers, mi-
crobial transglutaminase, and nanoparticles) are major
environmental factors for autoimmune disease. Our article and
this hypothesis support the formation of an “Autoimmune
Disease Food Pyramid.” The ideal diet for autoimmune disease
is still being determined; however, an increasing amount of
research is becoming available to formulate the beginnings of
an “Autoimmune Disease Food Pyramid” as a public health
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Dietary Strategies for the Prevention
and Management of Autoimmune Disease
From our knowledge, combining the following strategies are
novel and the first of its kind. Based on the available research, it
can be suggested that a diet that can control autoimmune disease
needs to improve the balance of intestinal microbiota, modulate
intestinal integrity, reduce inflammation, and regulate the im-
mune response. These dietary strategies apply to individuals
who are susceptible to autoimmune disease or who have estab-
lished autoimmune disease. The foundation of such a diet re-
quires the combination of whole foods and dietary strategies that
reduce arachidonic acid consumption to *90 mg per day (57–
195 g of animal products daily; Table 2). The exception to this is
when the PUFAs DHA and EPA are found naturally higher
within the food item, such as seafood, including salmon and
In addition, maintaining a ratio of *1–4:1 of omega-6:
omega-3 in the diet is suggested for human health.
more, reducing omega-6 PUFA, namely linoleic acid, can sup-
port the balance of microbiota where diets high in omega-6
PUFA have been found to increase intestinal microbes that drive
some inflammatory bowel diseases, such as colitis.
Complete avoidance of gluten-containing products is sug-
gested for individuals diagnosed with an autoimmune disease
as gluten has been shown to have a triple negative effect. First,
gluten activates zonulin causing increased intestinal perme-
Second, gluten stimulates enterocytes to release in-
flammatory mediators, such as IL-8 and arachidonic acid,
contributing to inflammation-induced dysbiosis.
Third, the
exposure of gluten to the immune system can potentially result
in immunologic cross-reactions, or molecular mimicry. In this
case, gluten is recognized as foreign, or as an autoantigen,
leading to the induction of autoimmunity.
High dietary long-chain saturated fats have been shown to
increase intestinal permeability,
contribute to dysbiosis,
and increase intestinal inflammation.
Therefore, limiting the
intake of long-chain saturated fat to <10% has the potential to
reduce these detrimental effects on the intestinal system. Fruit
and vegetable intake greater than six servings daily has been
associated with reduced inflammation.
Therefore, it is sug-
gested that the intake of fruit and vegetables be greater than
six servings per day to decrease inflammation in susceptible
individuals. Furthermore, it is suggested that fiber intake be
maintained at or >25–30 g per day, along with prebiotic
sources (e.g., asparagus, leeks, bananas, onions, garlic, and
cabbage) to support microbiota production and diversity.
Fermented foods, such as kefir, yogurt, kimchi, or fermented
soy milk, have been suggested to support the diversity of
the microbiota.
Although more research is required on
fermented foods, numerous studies have demonstrated the
effectiveness of supplemental probiotics on autoimmune dis-
Some fermented foods, such as “alive” sauerkraut,
have been reported to contain concentrations of various bac-
teria, for example, Lactobacillus spp., that are well above that
of probiotic supplements.
Reducing sodium may limit in-
duction of Th17 cells and the potential exacerbation of auto-
immune disease.
There is no current set limit for sodium
consumption for individuals with autoimmune disease; there-
fore, until further research verifies the ideal amount, consum-
ing <2300 mg of sodium daily is suggested. During acute
autoimmune disease flares or until intestinal integrity is re-
stored, limiting intake of foods containing dietary antigens,
such as gluten, milk, soybean, corn, tomato, and foods high in
lectins is advised. This reduces the potential risk of molecular
mimicry of these dietary antigens.
There are a number of supplements and dietary foods that
may be used in the management of autoimmune disease that
may potentially regulate the immune system or reduce inflam-
mation. Such nutrients and foods include vitamin D,
and particular strains of probiotics.
clinical benefits and increased treatment effectiveness are ex-
perienced when the diet is modified alongside supplementation,
compared with supplementation alone.
Diet and environ-
mental factors can still influence any number of the modifiable
risk factors of autoimmune disease. Nevertheless, every person
has individual needs and their autoimmune disease may mani-
fest in a unique manner and should always be referred to a
qualified professional (e.g., medical practitioner, nutritionist,
and naturopathic doctor) for dietary and prescription advice.
Particular diets, or components of such diets, have been
shown to influence digestive health and potentially impact the
development and progression of autoimmune disease. Com-
bining diets that include and exclude particular components is
suggested to support digestive health and modulate autoimmune
disease development and progression, forming the foundations
of the “Autoimmune Disease Food Pyramid.” These founda-
tions include reducing arachidonic acid consumption to <90 mg
per day, avoiding gluten-containing products, restricting long-
chain saturated fats, consuming required fiber intake, incorpo-
rating fermented foods, increasing fruit and vegetable intake to
above six portions daily and moderating sodium consumption.
Adherence to an“Autoimmune Disease Food Pyramid”may lay
the foundations to modulate autoimmune disease risk factors,
such as dysbiosis, intestinal integrity/permeability, and inflam-
mation, thereby managing or preventing autoimmune disease.
From here, further research is suggested to increase under-
standing of the use of food and dietary components in the
management and prevention of autoimmune disease, such as
reduced sodium and long-chain saturated fats, increased fiber,
and the beneficial probiotic effects of fermented foods.
B.L. would like to acknowledge the support of the Australian
Government Research Training Program Scholarship and the
Endeavour Summer Research Project Scholarship.
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Author Disclosure Statement
No competing financial interests exist.
Funding Information
No funding was received for this article.
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Bradley Leech, BHSc, is a clinical nutritionist and PhD candidate at the
Australian Research Centre in Complementary and Integrative Medicine. He is
also a clinic supervisor at the Endeavour College of Natural Health and subject
coordinator at the University of Technology Sydney. Bradley McEwen, PhD,
MHSc, is a naturopath, nutritionist, educator, and researcher. He is adjunct
senior lecturer in the School of Health and Human Sciences, Southern Cross
University. Eric Owusu Sekyere, PhD, MSc, is a science educator and re-
searcher. He is a senior lecturer in the department of bioscience, Endeavour
College of Natural Health.
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... For instance, early-life exposure to infections, vaccines (39), and dietary components (40) mold the immunological memory, consequently shaping how the immune system responds to exogenous stimuli later in life (41,42). During the recent decades, the tremendous increase in the prevalence of autoimmune conditions coincides with evolving dietary and hygiene styles in Westernized societies (43), indicating a strong influence of environmental factors on autoimmunity (44)(45)(46)(47)(48)(49). This is particularly important during pandemic eras since the emergence of unprecedented infections such as COVID-19 is thought to predominate among immunocompromised individuals such as those with preexisting autoimmune conditions who are also at an increased risk of COVID-19 related hospitalization (50). ...
Full-text available
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Bisphenol S (BPS), an analogue of the controversial bisphenol A (BPA) that is found in epoxy resins and plastics, is a potential endocrine-disrupting chemical that can mimic endogenous hormone signaling. However, little is known about the behavioral or immunologic effects of BPS. The purpose of this study was to examine the impact of diets in BPS-treated mice in relation to hyperglycemia, development of type 1 diabetes, immunomodulation, and behavioral changes. Adult male and female nonobese diabetic excluded flora (NODEF) mice were exposed to environmentally relevant doses of BPS (VH, 30, or 300 µg/kg BW) and fed either a soy-based diet, a phytoestrogen-free diet, or a Western diet. NODEF male mice fed a soy-based diet exhibited a decreased curiosity/desire to explore, and possibly increased anxiety-like behavior and decreased short-term memory when exposed to BPS (300 µg/kg BW). In addition, these mice had significant increases in non-fasting blood glucose levels along with increased insulin sensitivity, impaired glucose tolerance, resistance to fasting and proinflammation. Although BPS had little effect on the glucose parameters in NODEF male mice fed a Western diet, there were decreases in %CD24+CD5+ and %B220+CD40L- cell populations and increases in distance traveled during the novel object test, suggesting hyperactivity. NODEF females fed a phytoestrogen-free diet exhibited slight decreases in time spent immobile during the tail suspension test in both the 30 and 300 µg/kg BW dose groups along with increases in %CD4+CD8+ and %Mac3+CD45R+ cell populations, signifying increased hyperactivity and anxiety-like behavior. In conclusion, BPS-exposed NODEF mice exhibited sex and diet-related changes in hyperglycemia, behaviors and immune endpoints.
Modeling of food transport and absorption inside the small intestine is essential to better understand the digestive process as a whole. The models described by our paper present a method to visualize transport of a mass of food representing a bolus from the pylorus to the edge of the ileum. We have developed an integrated model to demonstrate passage of the bolus through the small intestine as well as the absorption of nutrients from it. We also aim to briefly discuss the importance of intestinal modeling, the models that have been developed including those we have based our own models on, and limitations of intestinal modeling as opposed to in vivo studies. Finally, we discuss future directions that intestinal modeling researchers can explore, such as inclusion of other organs within the digestive system and more specific modeling applying to different types of foods.
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Recent evidence regarding celiac disease has increasingly shown the role of innate immunity in triggering the immune response by stimulating the adaptive immune response and by mucosal damage. The interaction between the gut microbiota and the mucosal wall is mediated by the same receptors which can activate innate immunity. Thus, changes in gut microbiota may lead to activation of this inflammatory pathway. This paper is a review of the current knowledge regarding the relationship between celiac disease and gut microbiota. In fact, patients with celiac disease have a reduction in beneficial species and an increase in those potentially pathogenic as compared to healthy subjects. This dysbiosis is reduced, but might still remain, after a gluten-free diet. Thus, gut microbiota could play a significant role in the pathogenesis of celiac disease, as described by studies which link dysbiosis with the inflammatory milieu in celiac patients. The use of probiotics seems to reduce the inflammatory response and restore a normal proportion of beneficial bacteria in the gastrointestinal tract. Additional evidence is needed in order to better understand the role of gut microbiota in the pathogenesis of celiac disease, and the clinical impact and therapeutic use of probiotics in this setting.
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FOXP3+ Tregs are central for the maintenance of self-tolerance and can be defective in autoimmunity. In multiple sclerosis and type-1 diabetes, dysfunctional self-tolerance is partially mediated by a population of IFNγ-secreting Tregs. It was previously reported that increased NaCl concentrations promote the induction of proinflammatory Th17 cells and that highsalt diets exacerbate experimental models of autoimmunity. Here, we have shown that increasing NaCl, either in vitro or in murine models via diet, markedly impairs Treg function. NaCl increased IFNγ secretion in Tregs, and reducing IFNγ — either by neutralization with anti-IFNγ antibodies or shRNA-mediated knockdown — restored suppressive activity in Tregs. The heightened IFNγ secretion and loss of Treg function were mediated by the serum/glucocorticoid-regulated kinase (SGK1). A high-salt diet also impaired human Treg function and was associated with the induction of IFNγ-secreting Tregs in a xenogeneic graft-versus-host disease model and in adoptive transfer models of experimental colitis. Our results demonstrate a putative role for an environmental factor that promotes autoimmunity by inducing proinflammatory responses in CD4 effector cells and Treg pathways.
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Objectives: Habitual diet plays a major role in shaping the composition of the gut microbiota, and also determines the repertoire of microbial metabolites that can influence the host. The typical Western diet corresponds to that of an omnivore; however, the Mediterranean diet (MD), common in the Western Mediterranean culture, is to date a nutritionally recommended dietary pattern that includes high-level consumption of cereals, fruit, vegetables and legumes. To investigate the potential benefits of the MD in this cross-sectional survey, we assessed the gut microbiota and metabolome in a cohort of Italian individuals in relation to their habitual diets. Design and results: We retrieved daily dietary information and assessed gut microbiota and metabolome in 153 individuals habitually following omnivore, vegetarian or vegan diets. The majority of vegan and vegetarian subjects and 30% of omnivore subjects had a high adherence to the MD. We were able to stratify individuals according to both diet type and adherence to the MD on the basis of their dietary patterns and associated microbiota. We detected significant associations between consumption of vegetable-based diets and increased levels of faecal short-chain fatty acids, Prevotella and some fibre-degrading Firmicutes, whose role in human gut warrants further research. Conversely, we detected higher urinary trimethylamine oxide levels in individuals with lower adherence to the MD. Conclusions: High-level consumption of plant foodstuffs consistent with an MD is associated with beneficial microbiome-related metabolomic profiles in subjects ostensibly consuming a Western diet. Trial registration number: This study was registered at clinical as NCT02118857.
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Paleolithic nutrition, which has attracted substantial public attention lately because of its putative health benefits, differs radically from dietary patterns currently recommended in guidelines, particularly in terms of its recommendation to exclude grains, dairy, and nutritional products of industry. We evaluated whether a Paleolithic nutritional pattern improves risk factors for chronic disease more than do other dietary interventions. We conducted a systematic review of randomized controlled trials (RCTs) that compared the Paleolithic nutritional pattern with any other dietary pattern in participants with one or more of the 5 components of metabolic syndrome. Two reviewers independently extracted study data and assessed risk of bias. Outcome data were extracted from the first measurement time point (≤6 mo). A random-effects model was used to estimate the average intervention effect. The quality of the evidence was rated with the use of the Grading of Recommendations Assessment, Development and Evaluation approach. Four RCTs that involved 159 participants were included. The 4 control diets were based on distinct national nutrition guidelines but were broadly similar. Paleolithic nutrition resulted in greater short-term improvements than did the control diets (random-effects model) for waist circumference (mean difference: -2.38 cm; 95% CI: -4.73, -0.04 cm), triglycerides (-0.40 mmol/L; 95% CI: -0.76, -0.04 mmol/L), systolic blood pressure (-3.64 mm Hg; 95% CI: -7.36, 0.08 mm Hg), diastolic blood pressure (-2.48 mm Hg; 95% CI: -4.98, 0.02 mm Hg), HDL cholesterol (0.12 mmol/L; 95% CI: -0.03, 0.28 mmol/L), and fasting blood sugar (-0.16 mmol/L; 95% CI: -0.44, 0.11 mmol/L). The quality of the evidence for each of the 5 metabolic components was moderate. The home-delivery (n = 1) and dietary recommendation (n = 3) RCTs showed similar effects with the exception of greater improvements in triglycerides relative to the control with the home delivery. None of the RCTs evaluated an improvement in quality of life. The Paleolithic diet resulted in greater short-term improvements on metabolic syndrome components than did guideline-based control diets. The available data warrant additional evaluations of the health benefits of Paleolithic nutrition. This trial was registered at PROSPERO ( as CRD42014015119. © 2015 American Society for Nutrition.
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Despite tremendous growth in the consumption of gluten-free (GF) foods, there is a lack of evaluation of their nutritional profile and how they compare with non-GF foods. The present study evaluated the nutritional quality of GF and non-GF foods in core food groups, and a wide range of discretionary products in Australian supermarkets. Nutritional information on the Nutrition Information Panel was systematically obtained from all packaged foods at four large supermarkets in Sydney, Australia in 2013. Food products were classified as GF if a GF declaration appeared anywhere on the product packaging, or non-GF if they contained gluten, wheat, rye, triticale, barley, oats or spelt. The primary outcome was the ‘Health Star Rating’ (HSR: lowest score 0·5; optimal score 5), a nutrient profiling scheme endorsed by the Australian Government. Differences in the content of individual nutrients were explored in secondary analyses. A total of 3213 food products across ten food categories were included. On average, GF plain dry pasta scored nearly 0·5 stars less ( P < 0·001) compared with non-GF products; however, there were no significant differences in the mean HSR for breads or ready-to-eat breakfast cereals ( P ≥ 0·42 for both). Relative to non-GF foods, GF products had consistently lower average protein content across all the three core food groups, in particular for pasta and breads (52 and 32 % less, P < 0·001 for both). A substantial proportion of foods in discretionary categories carried GF labels (e.g. 87 % of processed meats), and the average HSR of GF discretionary foods were not systematically superior to those of non-GF products. The consumption of GF products is unlikely to confer health benefits, unless there is clear evidence of gluten intolerance.
Sodium intake in the United States exceeds recommended amounts across all age, gender and ethnic groups. National dietary guidelines advocate reduced intake by at least 1,000 mg per day or more, but whether there is population-wide benefit from further reductions to levels of 1,500 mg per day remains controversial. A brief review of current evidence-based dietary guidelines is provided and key prospective, randomized studies that report dietary and urinary sodium data are summarized. Dietary sources of sodium and eating patterns that offer nutritiously sound approaches to nutrient dense, reduced sodium intake are compared. No studies suggest that high sodium intake at the levels of the population's current diet is optimal. On the contrary, national and international evidence and systematic reviews consistently recommend reducing sodium intake overall, generally by 1,000 mg/day. Recommendations to reduce intakes to 2,400 mg/day are generally accepted as beneficial. Whether further reductions to 1,500 mg/day are useful, feasible and safe among specific subgroups in the population who are at increased risk of hypertension or stroke remains controversial and requires individualized consideration by patients and their health care providers. Copyright © 2015 Elsevier Inc. All rights reserved.
Multiple sclerosis (MS) is a debilitating autoimmune neuroinflammatory disease influenced by genetics and the environment. MS incidence in female subjects has approximately tripled in the last century, suggesting a sex-specific environmental influence. Recent animal and human studies have implicated dietary sodium as a risk factor in MS, whereby high sodium augmented the generation of T helper (Th) 17 cells and exacerbated experimental autoimmune encephalomyelitis (EAE), the principal model of MS. However, whether dietary sodium interacts with sex or genetics remains unknown. Here, we show that high dietary sodium exacerbates EAE in a strain- and sex-specific fashion. In C57BL6/J mice, exposure to a high-salt diet exacerbated disease in both sexes, while in SJL/JCrHsd mice, it did so only in females. In further support of a genetic component, we found that sodium failed to modify EAE course in C57BL6/J mice carrying a 129/Sv-derived interval on chromosome 17. Furthermore, we found that the high-sodium diet did not augment Th17 or Th1 responses, but it did result in increased blood-brain barrier permeability and brain pathology. Our results demonstrate that the effects of dietary sodium on autoimmune neuroinflammation are sex specific, genetically controlled, and CNS mediated.-Krementsov, D. N., Case, L. K., Hickey, W. F., Teuscher, C. Exacerbation of autoimmune neuroinflammation by dietary sodium is genetically controlled and sex specific.
This review will focus on the pathogenesis, clinical manifestations, diagnosis, and management of celiac disease (CD). Given an increasing awareness of gluten-related disorders, medical professionals of all varieties are encountering patients with a diagnosis of CD or who are thought to have food intolerance to gluten. The prevalence of CD among the general population is estimated to be 1% in Western nations, and there is growing evidence for underdiagnosis of the disease, especially in non-Western nations that were traditionally believed to be unaffected. The development of serologic markers specific to CD has revolutionized the ability both to diagnose and monitor patients with the disease. Additionally, understanding of the clinical presentations of CD has undergone a major shift over the past half century. Although it is well understood that CD develops in genetically predisposed subjects exposed to gluten, the extent of other environmental factors in the pathogenesis of the disease is an area of continued research. Currently, the main therapeutic intervention for CD is a gluten-free diet; however, novel nondietary agents are under active investigation. Future areas of research should also help us understand the relationship of CD to other gluten-related disorders. Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.