Diet, inflammation and the microbiome
A “westernized” diet, including higher animal fat and animal products,
increased sugar and ultra-processed foods and overconsumption of
calorie-dense, low nutrient and low fiber foods appears to be an
important factor in increasing disease rates in many countries around
the world[39,40]. Allergic and autoimmune diseases have increased
along with the adoption of this diet, but so have cardiovascular
diseases, diabetes, obesity and chronic lung diseases[41,42]. This
suggests that diet may be playing an important role in these diseases.
This is supported by interventional studies in type 2 diabetes mellitus
and cardiovascular disease [43,44]. Diet also appears to play a
significant role in COPD[45].
Interleukin-6 (IL-6) and C-reactive protein (CRP) are correlated with
obesity[46]. CRP has been found to decrease with weight loss
independently of the type of diet or weight loss method[47]. Studies
have found that the traditional Mediterranean diet, in particular,
lowers IL-6, with part of its effect being independent of weight
loss[48]. Dietary approaches to stop hypertension (DASH), emphasizes the consumption of low fat, whole foods. The DASH approach has been found to be effective
in reversing cardiovascular disease and hypertension[44,49]. Another
study showed that a diet with reduced saturated fat and increased fiber,
combined with exercise, prevented diabetes in a proportion of patients
in a randomized controlled trial of pre-diabetics[50]. Vegetarian or
plant-based diets have shown benefit in cardiovascular disease[44]
and other inflammatory diseases[51], including inflammatory
arthritis[52]. Vegetarian and vegan diets appear to be generally
safe, if vitamin B12 is supplemented and adequate attention is paid to
other potentially deficient nutrients[53]. Diets that tend to
emphasize fruits and vegetables and reduce processed meats and added
sugar are associated with better outcomes with regard to lung function
in COPD[45]. Typically, these diets cause changes in the microbiota
that are beginning to be explored[54]. All tend to increase
consumption of fiber, which many studies have found to affect short
chain fatty acid production[55] and immune function[5].
Ruminococcus gnavus, a commensal microbe in the intestinal tract, was
recently found to be potentially involved in contributing to
inflammatory arthritis[56] and inflammatory bowel disease[57].
This may be due to several characteristics, including its ability to
degrade mucus, which enhances its translocation across a weakened
epithelial barrier. R. gnavus is also increased in those with coronary
artery disease[58] and has been found to be decreased by a higher
fiber, lower sugar Mediterranean diet[59]. A mutated clade of R.
gnavus that tolerates a high-oxygen, pro-inflammatory environment in the
intestinal tract has been identified in inflammatory bowel
disease[60].
Enterococcus gallinarum, another commensal microbe with pathogenic
potential, has been implicated in systemic lupus erythematosus[61].
E. gallinarum can cause disease in a lupus mouse model when the
intestinal barrier is weakened, as can happen as a result of dietary
factors, certain drugs, hyperglycemia and other factors[62].
There is evidence of a high-fat diet being associated with increases in
endotoxin-producing, gram negative Enterobacteriaceae[63].
Endotoxin, as well as the bacteria that produce it, can cross the
mucosal barrier of the gut and have systemic inflammatory effects. Lower
levels of fiber are thought to increase mucin degrading bacteria that
also increase intestinal permeability. Research indicates that this can
negatively affect immune function and, therefore, promote respiratory
diseases[63].
There is growing support for the view that many of the effects of diet
on health arise from the effects of different types of food on the
presence of pathogenic species or on the microbial balance in the
intestines and elsewhere[12,62,64]. Thus, dietary patterns can lead
to inflammation and the overabundance of inflammation-associated
microbes, including Enterobacteriaceae or fungal species, such as
Candida albicans, that have greater pathogenic potential. It has also
been proposed that microbes in food/beverages may have harmful or
beneficial effects, and microbes and other substances from
ultra-processed foods may be more likely to have harmful
effects[12].
The connection between the gut and lungs is increasingly apparent. One
example is a study that found Candida albicans overgrowth in the
intestinal tract had a negative effect on an inflammatory lung
disease[65]. C. albicans may overgrow due to antibiotic use,
excessive sugar and refined carbohydrates[66] or low-grade
inflammation[67]. Other interactions between the gut and lung
microbiotas have been discussed in recent reviews[4,68]
With regard to weight loss interventions, recent evidence from a
randomized controlled study of inpatient adults indicates that increased
consumption of ultra-processed foods is a key factor that leads to an
overconsumption of carbohydrates resulting in weight gain[69].
Whether a diet that focuses on reducing carbohydrates or reducing fat is
most beneficial, appears to vary between individuals as a result of
still undetermined factors[70]. In fact, recent research using
continuous blood sugar monitoring found that the precise foods that will
increase blood sugar most, and thus be more likely to cause significant
negative metabolic effects, differs among individuals[71,72]. Thus,
the best approach to maintaining an optimal weight and blood sugar level
may need to be personalized to some degree. However, a common theme in
the diet research is the need to favor whole plant foods, particularly
fruits and vegetables, and reduce ultra-processed food.
Recent research is showing the benefits of intermittent fasting,
time-restricted eating[73] and fasting mimicking diets[74,75].
One benefit of a time-restricted approach appears to be related to it
being typically more compatible with human circadian rhythms[76].
This approach may also facilitate reduction of overall caloric
intake[73] and may improve sleep[76].
Recently, a carefully-designed diet that restricts overall calories and
protein has been developed that is meant to be used for a period of 5
days every few months[77]. This fasting mimicking diet is designed
to be easier to follow, yet have most of the benefits of fasting or
caloric restriction. Studies suggest that it can increase stem cell
production and the beneficial process of autophagy with overall
beneficial effects on immune function[78]. There is also evidence
that it is beneficial with regard to insulin resistance and
diabetes[74] and has positive effects on the microbiota[79].
Besides these benefits and the benefit of weight loss programs in
general, there may be other advantages of these types of dietary
interventions. Food/beverages from a westernized diet, particularly high
levels of high-fat, processed animal products and ultra-processed, high
sugar/refined carbohydrate food, could cause imbalances in the
microbiome and be a direct or indirect source of increased levels of
pro-inflammatory, potentially pathogenic, microbes as discussed
above[12]. Thus, dietary interventions that reduce these
ultra-processed foods/beverages may help give the immune system a better
chance of reducing negative effects of these microbes.
Overall, the various dietary interventions discussed above appear to
reduce the tendency of a westernized diet to contribute to insulin
resistance, weight gain, microbial imbalances, infections and immune
dysregulation. The above research does not determine whether a
particular diet will be beneficial for avoiding severe disease from
COVID-19, but it does suggest interventions that could help improve and,
in some cases, prevent/reverse the diseases that are risk factors for
it. Some suggestions for research specific to COVID-19 will be discussed
near the end of this article.