Prebiotic research going beyond the gut

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The human body plays host to a greater number of bacteria and other microbes than the number of human cells. Estimates suggest that there are over 10 trillion bacteria living on or in the body, with the vast majority residing in the colon.¹ The gut is also where the majority of the immune system lies. Obviously, this interface of microbes with the immune system has a tremendous influence on health. Probiotic supplementation has traditionally been considered one means of influencing the gut microbiota, and by connection the human immune system, to achieve both local and systemic effects. However, current research points to prebiotics as another potent tool for favorably influencing the human microbial flora and supporting health.

Recently, the International Scientific Association for Prebiotics and Probiotics (ISAPP) defined a prebiotic as “a substrate that is selectively utilized by host microorganisms conferring a health benefit.”² Generally, prebiotic effects have been associated with various plant-based fibers; however, research is showing that there are other substances that also confer prebiotic benefits.

Studies are further highlighting several beneficial clinical outcomes associated with prebiotic intake, not only for digestive health but for other purposes including supporting metabolic, brain, and heart health. Some of the latest research is reviewed here.

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Yeast Metabolites for Healthy Gut Function

A unique, immune-enhancing fermentation product from the yeast Saccharomyces cerevisiae known as EpiCor (Embria Health Sciences; Ankeny, IA) has shown prebiotic properties in preliminary studies. With a recent double-blind, placebo-controlled pilot study, researchers led by Iris Pinheiro of ProDigest (Ghent, Belgium) aimed to investigate the prebiotic effects of EpiCor in 80 human subjects with gastrointestinal discomfort and reduced bowel movements.³

Participants were classified into two groups based on symptom severity: severe and moderate. EpiCor or placebo was administered at a daily dose of 500 mg for 6 weeks after a two-week run-in period. Fecal samples were collected at baseline, 3 weeks, and 6 weeks, and subjective measures of constipation-associated quality of life and general perceived stress were also assessed.

In the moderate-symptom subgroup, EpiCor led to a significant reduction in general digestive symptoms, bloating, and feelings of fullness. Stool consistency significantly improved in the total population after two weeks of Epicor supplementation. Constipation-related quality-of-life and general perceived-stress scores also improved in those taking EpiCor.

Bowel movement frequency showed improvement, nearly reaching statistical significance in the total group. Beneficial changes to the bacterial composition of the microbiome were noted on stool analysis, including an increase in members of the Bacteroidaceae and Prevotellaceae groups in the severe-symptom subgroup, which are known to be deficient in constipated individuals. These findings suggest that a relatively low dose of EpiCor (500 mg/day) can confer prebiotic benefits and improve symptoms of digestive health.

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Appetite Regulation in Children

Inulins are a class of plant-based polysaccharides that are traditionally associated with prebiotic activity. A recent study aimed to explore the potential benefits of inulin in overweight and obese children related to its ability to improve appetite control.

In the randomized, double-blind, placebo-controlled trial, 42 children aged 7 to 12 supplemented with 8 g of oligofructose-enriched inulin per day or a placebo for 16 weeks.⁴ Appetite control was assessed using food records, energy intake, and fasting satiety hormone concentrations. Ratings on a visual analog scale were also taken from the children following a buffet breakfast. Caregivers completed Eating Behavior Questionnaires for the children.

Compared to the placebo group, those supplementing with prebiotics had significantly higher feelings of fullness and lower prospective food consumption after 16 weeks. Prebiotics also significantly reduced caloric intake at the week 16 breakfast in 11- to 12-year-olds compared to placebo, though this finding was not significant for 7- to 10-year-olds. Fasting levels of the satiety hormones ghrelin and adiponectin also increased significantly after 16 weeks in the prebiotic group compared to placebo, indicating that prebiotic supplementation with oligofructose-enriched inulin can help with appetite regulation in overweight children.

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Asthma and Airway Inflammation

As prebiotics influence the makeup of the gut microbiome, which interacts with our immune system, they have the potential to impact areas of the body outside of the digestive tract. A recent pilot study led by a group of UK researchers including Neil Williams from Trent University (Nottingham, UK) aimed to assess the effect of prebiotic supplementation on exercise-induced asthma, a condition associated with airway inflammation.⁵

In the study, 10 adults with asthma and exercise-induced bronchoconstriction and 8 healthy controls were randomized to supplement with 5.5 g of milk-derived galacto-oligosaccharides or placebo daily for three weeks. Participants underwent eucapnic voluntary hyperpnoea (EVH; considered an optimal test for diagnosing exercise-induced asthma that entails breathing in of dry air) at baseline and at the end of the study. In the group with exercise-induced asthma, the post-EVH fall in forced expiratory volume in 1 second (FEV1; a measure of lung function) was reduced by 40% as a result of supplementation with the prebiotic fiber but was unchanged in those taking placebo. Additionally, markers of airway inflammation, including TNF-α and CRP, were reduced in those with exercise-induced asthma symptoms, indicating potential beneficial effects of galacto-oligosaccharide supplementation for airway inflammation.

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Gut-Based Endothelial Support

Preliminary research in animals is beginning to highlight the link between certain prebiotics and cardiovascular health. Given that the microbiota influences so many aspects of systemic health, this is not surprising. In a recent study, European researchers created a mouse model that linked fatty liver and endothelial dysfunction by feeding the mice a diet deficient in omega-3 fatty acids for 12 weeks.⁶

For the last 15 days of the study, the researchers separated the mice into two groups and added inulin-derived fructo-oligosaccharides (FOS) to the diet of one group. They found that the mice fed the FOS prebiotics showed a complete reversal of endothelial dysfunction in gut mesentery and carotid arteries. The researchers found this benefit to be nitric oxide–mediated, as the prebiotic fiber induced favorable changes in the microbiota of the mice leading to an increase in the number of nitric oxide–producing bacteria and an accompanying decrease in bacteria involved in bile acid synthesis.

Furthermore, changes in gene expression in the gut and liver also occurred, which favored the preservation of endothelial function. If this holds true in human studies, supplementing with FOS may be a novel approach to preserving endothelial health and could lead to greater benefits for metabolic and cardiovascular health.

References:

1. Vemuri R et al. “Gut microbial changes, interactions, and their implications on human lifecycle: an ageing perspective.” BioMed Research International. Published online February 26, 2018.
2. Gibson GR et al. “Expert consensus document: The International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of prebiotics.” Nature Reviews. Gastroenterology & Hepatology, vol. 14, no. 8 (August 2017): 491-502
3. Pinheiro I et al. “A yeast fermentate improves gastrointestinal discomfort and constipation by modulation of the gut microbiome: results from a randomized double-blind placebo-controlled pilot trial.” BMC Complementary and Alternative Medicine. Published online September 4, 2017.
4. Hume MP et al. “Prebiotic supplementation improves appetite control in children with overweight and obesity: a randomized controlled trial.” American Journal of Clinical Nutrition, vol. 105, no. 4 (April 2017): 790-799
5. Williams NC et al. “A prebiotic galactooligosaccharide mixture reduces severity of hyperpnoea-induced bronchoconstriction and markers of airway inflammation.” British Journal of Nutrition, vol. 116, no. 5 (September 2016): 798-804
6. Catry E et al. “Targeting the gut microbiota with inulin-type fructans: preclinical demonstration of a novel approach in the management of endothelial dysfunction.” Gut, vol. 67, no. 2 (February 2018): 271-283