Michael Traub, ND, DHANP, FABNO

Tolle Causam

The comorbidity of skin disease and gastrointestinal (GI) disorders has long been recognized. In recent years, small intestinal bacterial overgrowth (SIBO) has been identified as an underlying problem in the majority of patients diagnosed with irritable bowel syndrome (IBS). It has been estimated that 10-20% of the population in the United States suffer from IBS, and that 84% of IBS patients have SIBO.¹ This 2-part article will review the current evidence basis for SIBO as a comorbid and contributory factor in several common skin diseases. Part 1 will explore the connection between SIBO and rosacea and acne. The evidence for a link between SIBO, rosacea, and acne is stronger than for any other skin conditions.

Part 2 of this article will cover SIBO and atopic dermatitis, urticaria, psoriasis, and systemic sclerosis.

Rosacea

Rosacea trigger factors are myriad including dietary; however, an association with GI disorders such as IBS is also very plausible. SIBO can explain many cases of IBS, and in 2 studies treatment of SIBO was shown to improve rosacea. The prevalence of SIBO in rosacea patient populations has been found to range from 46% to 66%.^2-4

In an Italian study of 113 consecutive rosacea patients and 60 controls, 52 of the 113 patients were found to have positive lactulose breath tests (LBT) for SIBO (as compared with 3 of 60 controls).³ Subjects were randomized and blinded and treated with rifaximin (1200 mg/d) (n=32) or placebo (n=20) for 10 days. Treatment normalized the LBT in 28/32 patients; 71% showed clearance of their rosacea, and 21% showed marked improvement. Their GI symptoms also decreased. Of those given placebo, 2/20 had their rosacea worsen, and the rest showed no change. When placebo-treated subjects were crossed over to treatment with rifaximin, 17/20 experienced a normalization of their LBT, and 15/17 had their rosacea clear. Thus, 45/52 patients experienced total eradication of rosacea using rifaximin. Improvement was maintained at 9 months in 96%. Two patients with recurrence were cleared with re-treatment.³

Similarly, a double-blind, controlled study showed that after SIBO eradication with antibiotic treatment, 71% of patients (28/32) had complete clearance of rosacea.² In contrast, patients treated with placebo had no change in rosacea symptoms or had a worsening of symptoms. Once the placebo patients were treated with antibiotic therapy, 75% of patients experienced a resolution of rosacea symptoms.²

These studies demonstrate that rosacea patients often have a significantly higher SIBO prevalence than non-­rosacea patients and that in a majority of patients, treatment and eradication of SIBO can significantly reduce rosacea symptoms.

Acne

Over 75 years have passed since dermatologists John Stokes and Donald Pillsbury proposed a gastrointestinal mechanism for the overlap between depression, anxiety, and skin conditions such as acne.⁵

They hypothesized that emotional states might alter the normal intestinal microbiota, increase intestinal permeability, and contribute to systemic inflammation.⁵ Among the remedies advocated by Stokes and Pillsbury were Lactobacillus acidophilus cultures. Citing research showing that as many as 40% of individuals with acne have hypochlorhydria, Stokes and Pillsbury hypothesized that less than adequate stomach acid would set the stage for migration of bacteria from the colon towards the distal portions of the small intestine, as well as an alteration of normal intestinal microflora. Many aspects of this gut-brain-skin unifying theory have recently been validated.⁶ The role of the intestinal microbiome, as well as oral probiotics to mediate systemic inflammation, oxidative stress, glycemic control, tissue lipid content and even mood, have important implications in acne.

Acne patients are at higher risk for GI distress. One study of more than 13 000 adolescents with acne showed they were also more likely to experience GI symptoms such as halitosis, gastric reflux, bloating, and constipation.⁷

In recent years it has been confirmed that hypochlorhydria is a significant risk factor for SIBO. Indeed, SIBO is detected via hydrogen breath testing in half of patients on long-term proton pump inhibitor treatment.⁸

Just as Stokes and Pillsbury had supposed, SIBO has recently been shown to be associated with increased intestinal permeability, whereas antimicrobial treatment of SIBO helps to restore the normal intestinal barrier.⁹ Experimental studies reveal that psychological stress stagnates normal small intestinal transit time, encourages overgrowth of bacteria, and compromises the intestinal barrier.¹⁰ SIBO is strongly associated with depression and anxiety, whereas eradication of SIBO improves emotional symptoms.¹¹ Oral administration of probiotics has also proven beneficial in the reduction of SIBO.¹²

The Role of Diet

Interestingly, the omega-3 fatty acid-rich cod liver oil advocated by Stokes and Pillsbury may have been ahead of its scientific time. Not only has an omega-3-deficient diet been shown to increase SIBO in animals,¹³ it has been linked in multiple human studies to an increased risk of depressive symptoms.¹⁴ A small series of case reports indicate the value of omega-3 fatty acids in both the clinical grade of acne and global aspects of well-being.¹⁵

In recent years it has become evident that there may be a connection between the risk of acne and dietary components, most notably low-fiber carbohydrates. For example, regional diets low in processed foods and sugars (with an overall low glycemic load) are associated with decreased acne risk.¹⁶ Intervention studies using similar low glycemic load meals have reported improvements in acne vulgaris.¹⁷

Of 3 large population studies linking dairy consumption (most notably skim milk) and acne, none found a positive correlation between fermented dairy (eg, yogurt) and acne.^18-20 It has been suggested that milk consumption is associated with acne because it contains growth hormones (both synthetically added and naturally occurring.²¹ Acne is driven by insulin-like growth factor 1 (IGF-1),²² and IGF-1 can be absorbed across colonic tissue.²³ It is interesting to note that probiotic bacteria (lactobacilli, in particular) utilize IGF-1 during the fermentation process when added to milk, with a resultant 4-fold lower level of IGF-1 in fermented vs skim milk.²⁴ If intestinal permeability is increased in acne, the intestinal absorption of IGF-1 would likely be enhanced in general, and more specifically when milk (rather than fermented dairy) is orally consumed.

Summary

The scientist and philosopher, Goethe, is quoted as saying, “Everything has been thought of before, but the difficulty is to think of it again.” Based on a review of the original hypotheses of Stokes, Pillsbury, and their peers, it seems that many of the recent investigations in the area of the gut-brain-skin axis, in the broad sense, have been thought of before. The difference is the degree of scientific sophistication, which now enables us to see an undeniable link between these major organ systems.

The lines of communication, as mediated by gut microbes, may be direct and indirect – ultimately influencing the degree of acne via a systemic effect on inflammation, oxidative stress, glycemic control, tissue lipid levels, pathogenic bacteria, and levels of neuropeptides and mood-regulating neurotransmitters. It was not the contention of Stokes and Pillsbury that acne is a disease of the gastrointestinal tract. Yet, there appears to be more than enough supportive evidence to suggest that gut microbes, and the integrity of the GI tract itself, are contributing factors in the acne process.

The comorbidity of SIBO with atopic dermatitis, urticaria, psoriasis and systemic sclerosis will be reviewed in Part 2 of this article, to be published in the next issue of NDNR.

References:

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Michael Traub, ND, DHANP, FABNO, was inspired by his dermatologist father to become the leading expert in dermatology in the naturopathic profession. Dr Traub has taught dermatology at 5 of the 7 accredited naturopathic medical schools in North America and is the author of the textbook Essentials of Dermatologic Diagnosis and Integrative Therapeutics. He has been medical director of Lokahi Health Center in Kailua Kona, HI, for the past 32 years. He has also been actively engaged in clinical research throughout most of his career. Dr Traub’s most recent investigation is the “Efficacy and Safety of Kamedis Eczema Treatment in Children and Adults with Atopic Dermatitis.”