A Genetic Link Between Antibacterial Response & IBD (TLR4)

Exercise

Exercise has been found to reduce TLR4 expression in humans and animals. Moderate exercise may be more beneficial for this purpose than short bursts of high-intensity exercise, which may produce more inflammation [R].

Broadly speaking, exercise may have a mild protective effect on the development of IBD; that is, people who are already physically active are somewhat less likely to develop Crohn’s than those who are sedentary [R].

Some people with severe IBD may not be able to exercise as strenuously as healthy peers. However, if the intensity of exercise is limited, then physical activity is believed to be beneficial for IBD patients. Physically fit people have less inflammation, a healthier immune response, lower weight, better mental health, and stronger bones [R, R, R].

If you have IBD, we recommend talking to your doctor about how much physical activity would be beneficial in your case.

Exercise may reduce TLR4 expression. If you have IBD, moderate exercise may be beneficial, but be careful not to overexert yourself.

Sun Exposure

In a clinical trial on 44 obese people, supplementation with vitamin D decreased blood TLR4 levels [R].

Crohn’s disease (and the steroids used to treat it) have been linked to calcium and vitamin D deficiencies and subsequent osteoporosis. Your doctor will monitor your vulnerability to these deficiencies, and if appropriate, prescribe supplements [R, R, R].

Sun exposure is one of the main ways that the body obtains vitamin D. If your doctor does not advise you to take supplements, you can get enough vitamin D from under an hour of sun [R].

Vitamin D deficiency is a risk during IBD treatment. If your doctor does not recommend supplements, sun exposure is the best way to get vitamin D.

Vitamin A Sufficiency

Vitamin A plays a central role in healthy communication between TLR4 and the gut flora [R].

Deficiency of vitamin A is somewhat common in IBD patients. Your doctor will monitor your vitamin and mineral levels and recommend supplements if necessary; otherwise, make sure to include vitamin A rich foods (like liver, sweet potato, spinach, and carrots) in your diet [R, R].

Broccoli Sprouts (Sulforaphane)

Cruciferous vegetables, which include broccoli, kale, brussels sprouts, and other related plants, are rich in a compound called sulforaphane which has been found to block TLR4 [R].

Sulforaphane has also been found to reduce gut inflammation and improve colitis symptoms in mice [R, R].

Sulforaphane-rich cruciferous vegetables are often cited as anti-inflammatory foods and recommended as part of a healthy diet. However, many sources warn against cruciferous vegetables for patients with IBD [R, R, R].

Some people with IBD may tolerate cruciferous vegetables better than others. These vegetables contain insoluble fibers that fall into the category of FODMAPs, which may be dietary triggers for some [R].

Sulforaphane is also available as a supplement for those who want to try it but avoid food sources.

Sulforaphane blocks TLR4 and may reduce gut inflammation, but cruciferous vegetables may be dietary triggers for some. Work with a doctor or nutritionist to determine whether they are safe for you.

Tea

Green tea is rich in catechins, including EGCG. In cell studies, EGCG decreased the expression of TLR4. In animals, EGCG also reduces many of the inflammatory markers associated with IBD. Some researchers have therefore suggested that green tea should be recommended to IBD patients; human trials are currently lacking [R, R].

Omega-3 Fatty Acids

Omega-3 fatty acids are healthy fats and among the unsaturated fats believed to block the activation of TLR4. Many nutritionists strongly recommend seeking out dietary sources, including fish and nuts [R, R].

In a clinical trial of 49 obese pregnant women, supplementation with omega-3 fatty acids (DHA and EPA) reduced the expression of TLR4 in body fat and the placenta. These fatty acids also lowered TLR4 levels in cells [R].

In one study, 4.2 grams of fish oil daily for 8 months reduced the symptoms of active mild-to-moderate ulcerative colitis [R].

However, a review of three clinical trials and 138 ulcerative colitis patients found no significant benefits of fish oil supplementation. The authors suggested further trials with improved fish oil formulation (enteric-coated capsules) [R].

An increased ratio of omega-3 fats to omega-6 fats is associated with reduced inflammation and reduced rates of IBD, including ulcerative colitis. The more omega-3 and the less omega-6 fatty acids people consumed the less likely they appeared to be to develop IBD. It is currently unclear whether omega-3 supplementation could help with existing cases of ulcerative colitis [R].

Omega-3 fatty acids decrease TLR4 expression and are often recommended to IBD patients as healthy dietary fats.

Curcumin

Curcumin is a popular anti-inflammatory compound that comes from turmeric. In mouse and cell studies, this compound blocked TLR4 and improved the symptoms of TLR4-induced gut inflammation [R].

In one small study, curcumin reduced the frequency of bowel movements, diarrhea, and stomach pain in people with Crohn’s disease after a month of daily supplementation [R].

At least two clinical studies so far have found a possible benefit for curcumin supplementation in ulcerative colitis, either alone or in combination with conventional medications. Remember to never combine supplements with medications without first discussing these combinations with your doctor [R].

Curcumin, a popular anti-inflammatory supplement, blocks TLR4 and may reduce gut inflammation in Crohn’s disease.

NAC

In animal studies, NAC reduced TLR4 expression as part of its anti-inflammatory effect [R, R].

NAC also reduced gut inflammation In 37 people with colitis, helping to reduce inflammatory substances like IL-8 [R].

In rats, NAC supplementation strengthened the intestinal barrier and boosted antioxidant defense [R].

Probiotics

Certain probiotic strains reduced TLR4 activation in animal studies. In rats with gut inflammation, a blend of B. longum, L. bulgaricus, and S. thermophilus decreased inflammation while blocking TLR4. L. jensenii had a similar effect in pigs [R, R].

Probiotics work by changing the composition of the gut flora, adding in beneficial species. As such, many strains are under investigation for their potential to improve gut disorders like IBD.

Some types of human gut bacteria, particularly Bacteroides and Prevotella species, produce compounds that suppress TLR4 signalling [R].

A meta-analysis of a blended probiotic containing Bifidobacteria, Lactobacillus, and Streptococcus species (VSL#3) found that remission rates rose by 1.7x in ulcerative colitis patients taking the probiotic compared to the placebo [R].

In animal models of IBD, the probiotic species that have produced positive results include L. plantarum, B. bifidum, and S. boulardii [R, R, R, R].

TLR4 has a close relationship with gut bacteria, and some probiotics may reduce TLR4 activation and improve the symptoms of IBD.

Ginseng

Some of the active compounds of ginseng appear to reduce the production of cytokines by decreasing TLR4 expression [R].

In animals, fermented wild ginseng reduced the severity of colitis, cytokine expression, and inflammation. In cell studies, the same fermented product reduced the production of inflammatory cytokines [R].

Skullcap

In cell studies, an active compound from skullcap called baicalin decreased inflammation by reducing the expression of TLR4 [R].

Human studies are lacking, but in animal studies, skullcap extracts reduced the severity of colitis and decreased intestinal permeability [R, R].

Cordyceps

In a clinical trial of 98 people with chronic kidney disease, supplementation with Cordyceps lowered the levels of TLR4 and other inflammatory markers. Its active compound cordycepin had similar effects in cells by directly blocking TLR4 signaling [R].

In a mouse study, Cordyceps sinensis extract reduced the symptoms of colitis, including weight loss, diarrhea, and bleeding. These effects have not been investigated in humans [R, R].

Other anti-inflammatory supplements that may block TLR4 and reduce gut inflammation include ginseng, skullcap, and cordyceps. Human studies are lacking for these possible effects.