Interview with Professor Emeran Mayer – The microbiome-gut-brain interaction and its significance in obesity

Monday, Oct 10, 2016

  • The role of the microbiome-gut-brain axis in infant and childhood obesity
  • Recommended dietary interventions to modulate the gut microbiome for optimal weight management
The gut, brain and the microbiome communicate via complex signalling mechanisms and emerging studies have implicated a role for this system in energy management of the host. We recently had the pleasure to speak to world authority and leading researcher in brain-gut relationships, Professor Emeran Mayer, who is currently Director of the Center for Neurobiology of Stress at the University of California, Los Angeles, USA. In this interview, Professor Mayer discusses how alterations in the microbiome-gut-brain axis contribute to the development of obesity and shares dietary recommendations for optimal weight management in infants and children.

Professor Emeran Mayer
Professor and Director
Center for Neurobiology of Stress
Division of Digestive Diseases
David Geffen School of Medicine at UCLA
CA, USA

 


 

EM: Professor Emeran Mayer
R: Reporter

R: How do the brain and gut affect each other, and what is the role of the gut microbiome in these interactions?

EM: The gut-brain axis is a bidirectional communication system which is critical for preserving health and homeostasis. The brain sends signals to the gut via the autonomic nervous system and the hypothalamic-pituitary-adrenal axis, and modulates an array of immune and gastrointestinal functions including motility and gastric acid secretion.1

Emotional signals such as anxiety, anger and fear also descend from the brain and cause the gut to respond in a manner akin to how emotions are conveyed by facial expressions.1 The gut, on the other hand, sends information regarding luminal content to the brain via nerve fibers closely linked to immune and enteroendocrine cells.1

The past decade has seen much interest in the role of the microbiota in maintaining gut-brain interactions. The intestinal microbiome is known to receive signals from the brain and the enteric nervous system of the gut. This results in the production of hundreds of thousands of metabolites, many of which end up in the systemic circulation to influence physiological and mental health.

The gut microbiota is the intermediary between the gut and brain, and the microbiota-brain-gut axis is likely to be the largest and most important regulatory system in the body. Disturbances to this system may cause a wide range of conditions, including functional gastrointestinal disorders (such as functional dyspepsia and irritable bowel syndrome) as well as inflammation in the gut and obesity.1
 

Disturbances to the [microbiome-brain-gut axis] may cause a wide range of conditions, including functional gastrointestinal disorders...inflammation in the gut, and obesity.
 

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R: How does the brain and gut respond differently to eating behaviours between normal-weight and overweight people?

EM: Under normal circumstances, hunger is controlled by the hypothalamus upon receiving signals from the gut in the form of appetite-regulating hormones such as ghrelin, as well as several satiety hormones, such as leptin or glucagon-like peptide-1 (GLP-1).

Ghrelin stimulates appetite when the stomach is empty and its action is opposed by satiety hormones. For overweight and obese people, the brain becomes less responsive to these signals and can independently drive pleasurable eating in the absence of an energy deficit, known as hedonic hunger. Hedonic hunger is propelled by images and smells of food which are prevalent in everyday life.

This regulatory system can also be altered by diet. An emerging animal study has shown that high-fat intake can reduce satiety signalling by disrupting the sensitivity of vagal nerves in the gut.2 Additives such as high-fructose corn syrup, which is abundant in many foods and beverages, has been shown to increase the levels of ghrelin in the blood and decrease the activity of satiety centres in the brain3, which enhances appetite.
 

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R: What is the significance of the gut microbiome in infant and childhood obesity, and do obese infants and children exhibit any common patterns in the composition of their gut microbiome?

EM: As the human genome has remained largely unchanged for generations, it is accepted that the current rise of obesity is primarily due to a modern lifestyle characterized by excessive calorie intake.

Recent evidence suggests that the gut microbiota is involved in energy homeostasis, body weight control and inflammation4, 5, and a diet high in energy-rich foods can disrupt the gut microbiota and potentially contribute to the pathophysiology of obesity. This is particularly significant in infant and children as the gut microbiota experiences rapid development during the first few years of life.6
 

The gut microbiota is involved in energy homeostasis, body weight control and inflammation; a diet high in energy-rich foods can disrupt the gut microbiota and potentially contribute to the pathophysiology of obesity.
 

Excessive intake of fats, whether in chronic amounts or even from a single meal, can alter the microbial ecosystem, including a higher proportion of gram-negative bacteria.

An altered gut composition resulting from a high-fat diet can induce an increase of the inflammatory substance lipopolysaccharides (LPS), which can contribute to obesity via mechanisms such as insulin resistance, body weight gain and adipose tissue production.7-9 High fat intake may also increase the permeability for LPS through the gut wall by disrupting the deposition of tight junction proteins.5, 9 Studies have shown a distinct difference in the gut microbiota composition between obese and lean children: those classified as obese exhibited a lower Bacteroidetes to Firmicutes ratio, and a higher amount of fecal Lactobacillus spp. and Staphylococcus spp. compared with lean children.10

While some studies have reported that obese humans exhibit a diminished richness in their gut microbiota compared with non-obese subjects11, it is currently unclear whether low microbiota diversity is a risk factor for, or a result of obesity.
 

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R: Are there any maternal circumstances/factors associated with infant and childhood obesity?

EM: The early colonization and establishment of the infant gut microbiome is strongly associated with interactions with the mother, including mode of birth, sterilization during delivery, maternal stress and breast feeding.

Studies have suggested that babies delivered via Caesarean section initially display a reduced colonization of beneficial bacteria, reduced bacterial richness and increased establishment of potentially pathogenic bacteria, which may increase the risk of developing various health problems, including obesity later in life.12; however, this stability and diversity eventually catches up with babies who are born vaginally.13 The evidence remains unclear and more research is required before any recommendations can be made.

Stress to the mother during pregnancy can also disrupt the normal composition of the vaginal microbiota, which can impact the initial bacterial colonization of the infant.14 Other maternal elements associated with childhood obesity include unhealthy lifestyle and dietary habits of the mother which are passed down to the offspring.
 

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R: What are the recommended early dietary interventions to modulate the gut microbiome for optimal weight management?

EM:

While dietary solutions for childhood obesity have yet to be established, natural approaches including prebiotics, probiotics and human milk oligosaccharides (HMOs) can modulate the gut microbiota and potentially improve metabolic function for optimal weight management.

Prebiotics are non-digestible foods that stimulate the growth of beneficial bacteria in the gut, the most common of which are oligosaccharides.15 A diet high in prebiotics can be achieved by eating a wide variety of plant-based foods. Studies have reported that African children on a diet high in plant-based foods have a more diverse gut microbiota than children in the West who consume large amounts of animal protein, sugar, starch and fat.16 The African children also exhibited a greater number of bacterial species which are able to break down prebiotic polysaccharides and carboxymethylcellulose into beneficial short-chain fatty acids (SCFAs).16 SCFAs are implicated in the harvesting of dietary energy, formation of adipose tissues, and gene expression of satiety hormones.17, 18 In addition to nutrition, SCFAs also exhibit anti-inflammatory properties by suppressing the production of pro-inflammatory molecules and inhibiting the recruitment of neutrophils and monocytes.19

Probiotics are live organisms which can produce health benefits for the host; the two most common bacterial genera found in commercial probiotic products include bifidobacteria and lactobacilli. While research on adults and children have suggested that the administration of probiotics may be beneficial in the treatment of obesity20, robust clinical studies are lacking and many questions remain unanswered, including which probiotic strains to give, optimal dosages and timing of administration. 

Human milk contains a mixture of bioactive substances including prebiotics, probiotics, proteins and sugars, all of which are important for maintaining an optimal gut microbiome. HMOs, which constitute a large proportion of human milk, increase the number of beneficial bacteria in the gut and facilitate the production of anti-inflammatory SCFAs, which are believed to contribute to weight and energy management.21 Although breastfeeding is the most suitable source of nutrition for the healthy infants, human milk is highly variable and it is unclear if maternal factors, such as weight and atopy21, can alter the composition of probiotics and the structure of HMOs in human milk, which can modulate the developing infant microbiota. 

Aside from nutritional benefits, suckling during breastfeeding also increases maternal oxytocin levels22, which promotes bonding between the infant and the mother. Nonetheless, mothers who are unable to breastfeed should provide their babies with formulas containing prebiotics, probiotics and HMOs which, as much as possible, resemble human milk.
 

Human milk oligosaccharides, which constitute a large proportion of human milk, increases the number of beneficial bacteria in the gut and leads to the production of anti-inflammatory short-chain fatty acids, which are believed to contribute to weight and energy management.


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PRACTICAL TIPS FOR HEALTHCARE PROFESSIONALS TO HELP REGULATE BODY WEIGHT IN INFANTS

  • Breastfeeding should be promoted whenever possible; however, mothers who are unable to feed the infant themselves or express human milk should provide their babies with formulas containing prebiotics, probiotics and HMOs, which closely resemble those of human milk  
  • Mothers – regardless of pregnancy status – and children should be encouraged to reduce their intake of animal fat, which are often ‘hidden’ in common foods, and consume a diet with a wide variety of vegetables, fruits and legumes that contain fiber and prebiotics
  • Naturally fermented foods such as kimchi, sauerkraut and miso are rich in probiotics and should be consumed for optimal colonization of beneficial bacteria. Dairy-based foods which contain commercial amounts of probiotics, such as yoghurt, are suitable for people of all ages and should be eaten on a regular basis
  • Aside from dietary interventions, portion control and regular physical activity are crucial for maintaining optimal weight

 

Summary:

The current obesity epidemic is generally attributed to a diet high in energy-rich foods. Emerging evidence points to the role of the microbiome-gut-brain axis in preserving health and homeostasis, and in the pathogenesis of obesity. This is especially relevant in infants and children as their early years of life is the most critical period for the development of a stable gut microbiota. While breastfeeding should always be the first choice for babies, dietary interventions with prebiotics, probiotics and HMOs may also be used to modulate an infant’s gut microbiome for optimal weight management; however, these alternative modalities raise many questions and more robust data are needed. Healthcare professionals should encourage parents and their children to adopt a healthy diet high in prebiotics and probiotics, and partake in regular physical activity for optimal weight management.
 

 


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References

  1. Mayer EA. Nat Rev Neurosci 2011;12:453-466.
  2. Kentish S, et al. J Physiol 2012;590:209-221.
  3. Lowette K, et al. Front Nutr 2015;2:5.
  4. Festi D, et al. World J Gastroenterol 2014;20:16079-16094.
  5. Cani PD, et al. Diabetes 2008;57:1470-1481.
  6. Matamoros S, et al. Trends Microbiol 2013;21:167-173.
  7. Muccioli GG, et al. Mol Syst Biol 2010;6:392.
  8. Cani PD, et al. Diabetes 2007;56:1761-1772.
  9. Sanchez M, et al. Int J Environ Res Public Health 2015;12:162-175.
  10. Bervoets L, et al. Gut Pathog 2013;5:10.
  11. Verdam FJ, et al. Obesity (Silver Spring) 2013;21:E607-615.
  12. Munyaka PM, et al. Front Pediatr 2014;2:109.
  13. Clarke G, et al. Acta Paediatr 2014;103:812-819.
  14. Jasarevic E, et al. Endocrinology 2015;156:3265-3276.
  15. Slavin J. Nutrients 2013;5:1417-1435.
  16. De Filippo C, et al. Proc Natl Acad Sci U S A 2010;107:14691-14696.
  17. den Besten G, et al. J Lipid Res 2013;54:2325-2340.
  18. Conterno L, et al. Genes Nutr 2011;6:241-260.
  19. Vinolo MA, et al. Nutrients 2011;3:858-876.
  20. Paolella G, et al. World J Gastroenterol 2014;20:15518-15531.
  21. Koleva PT, et al. Nutrients 2015;7:2237-2260.
  22. Matthiesen AS, et al. Birth 2001;28:13-19.

 

WYE-EM-020-JAN-16


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