The human diet has a significant impact on the health of the host microbiome. The consumption of a typical western diet high in animal protein, fat, and sugar is associated with a dysbiotic microbiota, reduced short chain fatty acid (SCFA) production and predisposes individuals to a variety of diseases.^1,2 In contrast, a diet rich in non-digestible carbohydrates (NDCs) and prebiotic fibres creates a favourable environment for beneficial microbes and provides enzymes for microbes to utilise and ferment for energy.³

Arabinogalactan, an isolated NDC, is abundant in a variety of plants, including beans, leeks, pears, corn, and grains. Recent evidence has found a proprietary arabinogalactan extract from larch tree (ResistAidTM) to have a beneficial impact on host microbiome and immune function.^4,5

Dosing Recommendations

• Clinically effective dose: 1.5 g/day, up to 15 g/day^6,7
• Duration: 6 weeks
• Form: Proprietary arabinogalactan extract from larch tree (ResistAidTM)
• Drug interactions:
• Immunosuppressants: Theoretically, larch arabinogalactan might interfere with immunosuppression therapy due to immunostimulant effects.⁶
• Safe dosing:
  • Studies suggest doses up to 15 g/day are considered safe.⁷

 In a randomised, double-blind, crossover, placebo-controlled trial consisting of 2, 6-week, intervention periods, 30 adults were randomly assigned to consume 15 g/day of ResistAidTM or equivalent maltodextrin (control) for 6 weeks, followed by a 3 week washout period.⁷

The objective of this study was to investigate the effect of an arabinogalactan product (ResistAidTM) on the faecal microbiome and SCFAs and gastrointestinal tolerance in healthy adults. The dose was selected to increase daily fibre intake from the average intake of 16.9 g/day to the recommended adequate intake of 25 g/day for adult women and 38 g/day for adult men.

• At week 6, compared to placebo, ResistAidTM supplementation was found to:
• Increase Bacteroidetes and decrease Firmicutes
• Increase Bifidobacterium
• Increase gene abundance of the gut microbiome for α-L-rhamnosidase, β-fructosidase and levanase, as well as tricarboxylic acid and vitamin B6 biosynthesis pathways (based on 16S rRNA sequences)
• Reduce faecal isovaleric, valeric and hexanoic acids
• Cause no adverse changes in bowel habits, stool consistency, gastrointestinal tolerance symptoms, chemistry profile, metabolic panel, or vitals

Effects on Bacteroidetes and Firmicutes

Following 6 weeks of ResistAidTM supplementation the relative abundance of Bacteroidetes was greater and that of Firmicutes was lower compared to control (Figure 1). While the clinical significance of this ratio remains unclear, some studies report a positive association with certain physiological conditions, such as obesity and inflammatory bowel syndrome.^8,9

Figure. 1. Changes in the major phyla with ResistAidTM intervention compared to placebo at weeks 3 and 6.

Increased Beneficial Bifidobacterium

Bifidobacterium are among the first microbes to colonise the human gastrointestinal tract and are one major genera of bacteria that make up a healthy microbiota. Researchers found an increase of the relative abundance of Bifidobacterium with ResistAidTM intervention compared to placebo at week 3.

Increased Gene Abundance of α-L-rhamnosidase

Consumption of ResistAidTM demonstrated an increase in the gene abundance of α-L-rhamnosidase, an enzyme that can cleave the terminal α-L-rhamnose from flavonoid glycosides. This process cleaves glycosidic moieties that are important for the bioavailability and subsequent bio-efficacy of flavonoids (quercetin, hesperidin, rutin).

Researchers hypothesise that increases in α-L-rhamnosidase may be attributed to stimulating effect of arabinogalactan on Lactobacillus and Bifidobacterium genera that express this enzyme.

Decrease in Harmful Branched SCFAs

NDCs are fermented by bacteria in the colon that produce SCFAs are generally considered beneficial to the host. SCFA production is often reduced when dietary fibre intake is low, which results in the gut microbiota shifting its metabolism toward the use of proteins, leading to increased production of harmful metabolites such as branched SCFAs (BSCFAs), ammonia, amines, and indolic compounds.

Another noteworthy finding of this study was the decreased concentration of branched SCFAs (BSCFAs) after ResistAidTM supplementation compared to placebo, suggesting a reduction of protein fermentation.

Gastrointestinal Tolerance

Increased consumption of NDCs can result in gastrointestinal symptoms in some individuals, particularly bloating and excessive flatulence. This is due to their high fermentability in the large intestine.

As mentioned previously, there were no statistically significant differences between interventions regarding gastrointestinal symptoms (i.e., abdominal cramping, distention/bloating, burping, stomach rumbling, gas/flatulence, nausea, reflux, and vomiting). This evidence suggests that consumption of 15 g/day of ResistAidTM for 6 weeks is safe and well tolerated while also offering improvements in gastrointestinal microbiota.

Clinical Take-Aways:

Consumption of NDCs such as arabinogalactans are important to support a favourable gastrointestinal environment for the growth of beneficial microbes. The results from this study demonstrate that the gut microbiome composition and predicted functions can be modulated by ResistAidTM consumption, leading to benefits in metabolic parameters and the immune system. While the study uses 15 g/day of ResistAidTM, amounts of 1.5 g/day have been shown to have beneficial outcomes. Given that the vast majority of adults in Western countries do not meet the recommended daily intake of fibre, addition of ResistAidTM to a whole foods diet may offer a strategy in supporting microbiome health through improving fibre intake.

 

Reference List

1 - Sonnenburg ED, Sonnenburg JL. Starving our microbial self: the deleterious consequences of a diet deficient in microbiota-accessible carbohydrates. Cell Metabol. 2014;20(5):779-86.

2 - Wu GD, Chen J et al. Linking long-term dietary patterns with gut microbial enterotypes. Science. 2011;334(6052):105-8.

3 - Flint HJ, Scott KP et al. Microbial degradation of complex carbohydrates in the gut. Gut microbes. 2012;3(4):289-306.

4 - Robinson RR, Feirtag J, Slavin JL. Effects of dietary arabinogalactan on gastrointestinal and blood parameters in healthy human subjects. Journal of the American college of Nutrition. 2001;20(4):279-85.

5 - Dion C, Chappuis E, Ripoll C. Does larch arabinogalactan enhance immune function? A review of mechanistic and clinical trials. Nutrition & Metabolism. 2016;13(1):1-1.

6 - Udani JK. Immunomodulatory effects of ResistAid™: A randomized, double-blind, placebo-controlled, multidose study. J Am Coll Nutr. 2013;32(5):331-8.

7 - Chen O, Sudakaran S et al. Effect of arabinogalactan on the gut microbiome: A randomized, double-blind, placebo-controlled, crossover trial in healthy adults. Nutrition. 2021;90:111273.

8 - Scotti EBS, Sasso GL et al. Exploring the microbiome in health and disease: implications for toxicology. J Toxicol Res Appl. 2017;1:1–37.

9 - Castaner O, Goday A et al. The gut microbiome profile in obesity: a systematic review. Int J Endocrinol. 2018;2018:4095789.