Our new feature series highlights research that is of interest to those fascinated by the science of the gut microbiome, helping to connect the dots between research studies and real-world application.

Exercise and exercise induced bronchoconstriction

Exercise-Induced Bronchoconstriction (EIB) and the gut microbiome

This Research Spotlight introduces Exercise-Induced Bronchoconstriction, a physical response to exercise that is of concern to both athletes and recreational exercisers.

Read further to see how gut microbiome modulation could be adopted by athletes and exercisers.

What is EIB?

Exercise-Induced Bronchoconstriction (EIB) was first recognised in people with asthma in response to exercise in the 1960s, where forced expiratory volume (FEV1) was reduced with exercise duration of 5-10 minutes and fell below the resting level during and after the exercise.

The FEV1 reduction was a result of bronchoconstriction1. Later, it was found that environmental factors such as humidity and air temperature can affect EIB. demonstrating the significance that environment has for both the athletic population and general public2.

EIB is described as acute airway narrowing as a result of exercise (during or after), occurring in a large proportion of patients with asthma, as well as in patients not known to have asthma. The high prevalence of EIB in athlete populations is partly a response to the environmental conditions including pollution and air conditions.

EIB occurs as a result of drying of the airways, causing the release of inflammatory mediators. The condition can be treated pharmacologically using short-acting beta2 agonists or long-acting beta2 agonists. Non-pharmacological methods are often used to minimise occurrence, these include warm-ups using a scarf or face mask to humidify the air, losing weight if necessary, improving overall fitness levels or modifying dietary intake3.

Population effects of EIB

The prevalence of EIB is between 5-20%, however the true prevalence is not known due to a lack of epidemiological studies differentiating between asthmatics and non-asthmatics. There is a high prevalence of Exercise-induced Bronchoconstriction in the asthmatic population because asthma is a comorbid factor for EIB, and 90% of asthmatics will experience EIB.

There is a greater prevalence of EIB in performance athletes compared to the general population due to inhalation of dry, cold air and air pollutants. There is also a higher prevalence of EIB in children, particularly children in urban environments compared to the general population4.

There is an effect on quality of life (QOL) in those who experience EIB due to the physical and emotional burden. Almost half the patients with asthma report that their participation and performance in sport is affected4. This has public health implications, as well as affecting the wider health of these patients. In turn, this demonstrates the need for effective management of EIB.

Managing EIB in patients with asthma

There are global guidelines to follow when seeing patients with asthma and this could be referred to for medications and other management options5.

Exercisers and athletes are additionally recommended to add a 10 to 15-minute moderate intensity warm-up as a ‘refractory period’ before the planned activity, to allow their body to adjust. Performance nutritionists need to be aware of the World Anti-doping Agency’s guidelines6, inform the athlete and encourage them to discuss the best option for them with their GP.

EIB and prebiotics

In the literature, Hyperpnoea-Induced Bronchoconstriction (HIB) is commonly referred to in place of EIB, due to it being a highly reproducible surrogate for EIB. Under laboratory conditions, HIB tends to be a simulation of EIB7.

Systemic inflammation can be part of asthma, whether that be a cause, an effect, or both is uncertain. Diet can reduce systemic inflammation, just as a Western Diet has been demonstrated to promote a pro-inflammatory environment, due to a lack of antioxidants and a surplus of saturated fatty acids, associated with immune activation8.

Systemic inflammation can be part of asthma, whether that be a cause, an effect, or both is uncertain. Diet can reduce systemic inflammation, just as a Western Diet has been demonstrated to promote a pro-inflammatory environment, due to a lack of antioxidants and a surplus of saturated fatty acids, associated with immune activation8.

Additionally, the gut microbiome can be responsible for metabolites that affect immune and metabolic responses.

Short chain fatty acids (SCFAs) are metabolites associated with immunomodulation and produced when prebiotic fibre found in fruit, vegetables, grains, legumes and pulses are fermented8. Whilst the dietary effect on asthma is inconclusive, a Western Dietary pattern appears to have a detrimental effect on asthma8.

Prebiotic supplements can be used when a person may find it difficult to include enough fibre in their diet. A prebiotic galactooligosaccharides (GOS) mixture, including Bimuno®, reduces severity of HIB, the surrogate for EIB, and markers of airway inflammation9.

This study highlighted in this Research Spotlight included 18 participants, of which 10 people with asthma were in the HIB group and 8 were in a control group, with no history of asthma.

Each group had five male participants and both groups were randomised for a crossover design to supplement with either Bimuno or placebo, with a 14-day washout period. The eucapnic voluntary hyperpnoea (EVH) method was used to cause a highly reproducible HIB in a laboratory setting9.

Bimuno supplementation reduced the severity of HIB, determined with reduced systemic Th2-driven inflammatory markers. Through its impact on the gut microbiome, this research suggests that Bimuno has the potential to modulate the underlying immunopathology of asthma, and thereby reduce hyper-responsiveness of the airways that is associated with HIB/EIB.

The precise mechanisms by which Bimuno modulates immune function and reduces airway inflammation is unclear and requires further exploration9.

Exercise and the immune system

The findings above suggest that prebiotic GOS supplementation can modulate the immunopathology of asthma, and since asthma can be exacerbated by exercise, there are other interactions to consider between exercise and immunity.

There is a J-shaped curve demonstrating the association between exercise training load and infection risk. At the highest training loads that performance athletes undertake, their infection risk is higher than those exercising at lower levels, particularly risk of upper respiratory tract infections (URTIs)10.

Similarly to how prebiotics reduce inflammation associated with EIB in the above example, nutrition appears to have immunological benefits in high exercise loads. Carbohydrate, protein and fluid intake are important in post-exercise recovery to prevent exercise-induced immune impairment.

While macronutrients play a role in recovery and immune modulation, micronutrients and non-nutritive food compounds including antioxidants can improve the inflammatory response to physiological stress in high exercise loads10.

Probiotics and prebiotics, as nutritional supplements used in athlete and non-athlete populations, have demonstrated reduced inflammation and less occurrence of URTIs during times of high exercise load10.

It seems apparent that a dietary pattern could be the ultimate recommendation for athletes to maintain optimal functioning of their immune system, whether that be related to URTIs or EIB. More research on diet and asthma, and using nutrition for health and performance in athletes, is more important than ever.

Infant gut microbiome: 2’-FL, Bimuno GOS and lactose

Infant gut microbiome: 2’-FL, Bimuno GOS and lactose

This Research Spotlight shares insight on Human Milk Oligosaccharides (HMOs), and their role in human health. The study looks at their prebiotic effect and influence on human health in comparison to Bimuno, a galactooligosaccharide (GOS) prebiotic.

The role of HMOs

Early colonisation of the gastrointestinal tract (GI tract), to form the gut microbiome, is important for the development of the immune system, metabolism and cognitive development. Colonisation of the GI tract by bacteria depends on the mode of delivery and type of feeding. Human breast milk provides the infant with bioactive compounds, including Human Milk Oligosaccharides (HMOs). These are structurally diverse carbohydrates that are highly abundant and specific to human milk - and have known health benefits. HMOs are resistant to digestion by intestinal enzymes and reach the colon where they act as prebiotics, nourishing beneficial gut bacteria.

Typical features of HMOs, such as their bifidogenic effect, modulatory effect on immune function and the gut barrier in infants, are thought to be equally beneficial to health in adulthood1. As a result, there is a growing interest in developing alternative sources other than breastmilk for HMOs. Comparison of their effects to the prebiotics on the market provides a realistic idea as to whether that is a commercially attractive approach.

In human breast milk, the most abundant HMO is 2′-fucosyllactose (2′-FL), which is available in large scale commercial production for use in infant formulas. The concentration of 2′-FL is highest in early lactation post-partum and selectively promotes the growth of bifidobacteria2.

Comparison of 2’-FL, Bimuno GOS and lactose

The study by Sallli et al. (2019) compared two prebiotics, 2’-FL and Bimuno GOS, with lactose, a simple sugar. The research looks at their effects on gut microbiota composition and short-chain fatty acids (SCFA) production. The primary role of lactose is to provide a readily available energy source to newborns and is normally absorbed before reaching the colon where the majority of gut bacteria reside.

While lactose is not a prebiotic, it is a simple sugar that bacteria will utilise. Salli et al (2019) modelled bacterial fermentation in the infant colon using the EnteroMIX® colon simulator. The study demonstrated that Bimuno GOS supports the growth of a wider range of beneficial microbes compared to 2′-FL. In comparison to 2’FL, GOS had promoted better growth of bifidobacteria and lactobacilli growth. In addition, GOS led to higher acetate and lactate production than 2′-FL2.

In another study, GOS resulted in a less diverse gut microbiota and SCFA production than 2′-FL; this creates a more homogenous gut microbiota, which is often preferred in infants. This was an outcome from Bimuno GOS supplementation, which may be due to the integral presence of HMOs, 3-galactosyl-lactose being the most abundant. This has been demonstrated to have a beneficial effect, such as anti-inflammatory effects when added to infant formula3. The addition of HMOs and GOS to the diet changes the metabolite profile in a matter of weeks. This is due to bifidobacteria being initial degraders of the HMOs in a cross-feeding interaction with butyrate producers like Clostridium coccoides or Eubacterium rectale as secondary degraders. Cross-feeding of HMOs in the adult gut microbiome improves gut barrier function. The research suggests using prebiotics, such as HMOs, to promote gut barrier function in adults1. More research is required in this area as it was carried out in vitro.

In Summary

The research by Salli et al., (2019) demonstrated that Bimuno GOS had a better prebiotic effect for the infancy early life stage and on SCFA production than 2’-FL. Not only does the research suggest a wider functionality of HMOs, but that Bimuno GOS has potential to promote gut barrier function in adults. However, it is recommended that further research is conducted in clinical trials to determine both mechanisms of action and efficacy.

β-Galactooligosaccharide with a Low FODMAP Diet improves IBS

β-Galactooligosaccharide with a Low FODMAP Diet improves IBS

This Research Spotlight introduces the low-FODMAP diet (LFD), how it can be helpful for people with IBS or functional gut disorders and where prebiotics can be beneficial to patients on a LFD. Read further to explore this study on the connections between IBS and dietary practices, particularly the low-FODMAP diet.

The prevalence of IBS

Globally, the prevalence of Functional Gastrointestinal Disorders (FGIDs) is as high as 40% and this includes Irritable Bowel Syndrome (IBS). IBS is a chronic FGID affecting Quality of Life (QoL) and health care use1. Although the exact pathophysiology of IBS is still unknown, genetic factors, the gut microbiome, gastrointestinal motility and enteric nervous system disturbances, visceral hypersensitivity and psychological distress are likely to play a role in combination2.

Due to a lack in understanding of the pathophysiology and individual variability of IBS, managing symptoms can be challenging. The Low-Fermentable Oligosaccharide, Disaccharide, Monosaccharide, and Polyol diet (low-FODMAP diet, LFD) is one approach, and has advantages in some patients, improving symptoms and QoL. However, downfalls of an LFD include that it is not a long-term solution, it is time intensive and can be detrimental to nutritional status of an individual2.

The LFD naturally leads to restriction of fructans and oligosaccharides in the diet, important complex carbohydrates with a prebiotic action. The restriction in an LFD may lead to a reduction in beneficial bacteria - and reductions in fecal bifidobacteria levels have been shown to relate to negative pain scores in IBS patients3. Based on the deleterious effects of the LFD on gut microbiota, other strategies should be explored3.

The role of prebiotics

Prebiotics, specifically Bimuno galactooligosaccharides (GOS), are shown to help reduce the symptoms of IBS similarly to the LFD diet. Prebiotic GOS Bimuno is selective to Bifidobacterium genus, that has a recognised capacity to support lower gut health, and support significant reductions to flatulence and bloating, along with improved stool consistency.

The reduction in flatulence was thought to be due to an increase in bifidobacteria as this does not produce gas4. Daily supplementation of Bimuno GOS is equally as effective as a LFD and in the short term, reduces flatulence, while increasing beneficial bacteria5. The research demonstrating Bimuno GOS to be equally as effective as the LFD was carried out in a population of individuals eating a Mediterranean diet, suggesting that those more accustomed to a diet higher in fibre may be more responsive to the prebiotic supplement5. Additionally, the combination of various therapies may have a beneficial effect to combine improved QoL and support the gut microbiota and gave reason for the research conducted by Wilson et al., (2020) investigating the use of Bimuno GOS in conjunction with the low-FODMAP diet.

Wilson et al., (2020) conducted a randomised, placebo controlled, three-arm trial on a cohort of 63 patients. A control sham diet with placebo supplement was compared to a low-FODMAP diet with placebo or LFD with 1.4g/day of Bimuno galactooligosaccharides (GOS) supplement over a 4-week period6. The sham diet restricts a similar number of foods as the LFD and is similarly difficult to follow, without affecting the intake of nutrients, fibre or FODMAPs6. The LFD combined with Bimuno GOS prebiotic produced a greater symptom response than the sham diet plus placebo, but addition of 1.4 g/d Bimuno GOS did not prevent the reduction of bifidobacteria. The low-FODMAP diet reduced faecal Actinobacteria and Butyrate, thus strict long-term use should not be advised.

The outcome of the study was  positive IBS symptom relief in ~70% of individuals in the LFD plus Bimuno group compared to 30% of subjects in the sham diet control group and 50% in the LFD plus placebo group. Individual IBS symptoms, including pain, distension/bloating and bowel dysfunction improved more markedly in the LFD plus Bimuno group compared to the sham diet control group, as well as a lower incidence and severity of abdominal pain and loose stools in the LFD plus Bimuno group compared to the sham diet control group.

In conclusion

Results of the study indicate that Bimuno GOS prebiotics are equally as good as the LFD in alleviating digestive discomfort related to IBS. The research points towards prebiotics – particularly Bimuno, the subject of the study – as a potential approach to managing IBS symptoms as an alternative to a low-FODMAP diet. Bimuno GOS is a powder supplement that fits easily into a daily routine and is supported by 100 scientific publications and over 20 clinical trials. Further research on Bimuno GOS and a LFD is encouraged to determine the potential to support the gut microbiota whilst on a LFD.

References

Exercise-Induced Bronchoconstriction (EIB) and the gut microbiome

  1. The Place of Physical Exercise and Bronchodilator Drugs in the Assessment of the Asthmatic Child
  2. Is there a unifying hypothesis for exercise- induced asthma?
  3. An Official American Thoracic Society Clinical Practice Guideline: Exercise-induced Bronchoconstriction
  4. Exercise-induced bronchoconstriction: prevalence, pathophysiology, patient impact, diagnosis and management
  5. Global Asthma Guidelines
  6. WADA
  7. Comparable reductions in hyperpnoea-induced bronchoconstriction and markers of airway inflammation after supplementation with 6·2 and 3·1 g/d of long-chain n-3 PUFA in adults with asthma 
  8. Diet and Asthma: Is It Time to Adapt Our Message?
  9. A prebiotic galactooligosaccharide mixture reduces severity of hyperpnoea-induced bronchoconstriction and markers of airway inflammation
  10. Immune nutrition and exercise: narrative review and practical recommendations

Infant gut microbiome: 2’-FL, Bimuno GOS and lactose

  1. Effects of Human Milk Oligosaccharides on the Adult Gut Microbiota and Barrier Function (nih.gov)
  2. The effect of 2′-fucosyllactose on simulated infant gut microbiome and metabolites; a pilot study in comparison to GOS and lactose | Scientific Reports (nature.com)
  3. Human Milk Oligosaccharides and Synthetic Galactosyloligosaccharides Contain 3′-, 4-, and 6′-Galactosyllactose and Attenuate Inflammation in Human T84, NCM-460, and H4 Cells and Intestinal Tissue Ex Vivo | The Journal of Nutrition | Oxford Academic (oup.com)

β-Galactooligosaccharide with a Low FODMAP Diet improves IBS

  1. Worldwide Prevalence and Burden of Functional Gastrointestinal Disorders, Results of Rome Foundation Global Study
  2. Irritable Bowel Syndrome and Dietary Interventions
  3. Controversies and Recent Developments of the Low-FODMAP Diet
  4. Clinical trial: the effects of a trans‐galactooligosaccharide prebiotic on faecal microbiota and symptoms in irritable bowel syndrome
  5. Effects of Prebiotics vs a Diet Low in FODMAPs in Patients With Functional Gut Disorders
  6. β-Galactooligosaccharide in Conjunction With Low FODMAP Diet...

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