The Mighty Microbiome

The ‘microbiome’ has become somewhat of a buzzword in the human biology and health world. But what is it exactly? Your microbiome is made up of all the microorganisms in your body which include bacteria, fungi and viruses. These largely exist on the surface of your skin and inside your large intestine. The diversity of microbes in this region begins to increase immediately from birth and is impacted by both the type of delivery and feeding method. The majority of these microorganisms play very important and beneficial roles in digestion and the general health of the gut. There are important bacteria such as Bifidobacteria which help in the digestion of breast milk or others which aid in the digestion of fibre, decrease triglyceride levels and prevent weight gain. Gut dysbiosis occurs when there is an imbalance between the healthy and pathogenic microbes in the gut. This can result in weight gain and an array of other microbiota related diseases.

Fun Fact: Microbiome vs Microbiota

Although used interchangeably, the microbiome refers to all of the microbial genomes that exist in an environment whereas the microbiota are all the microorganisms existing in an environment.

Subtle but significant!

Development of the gut microbiome from birth

Over the last few years, there has been an increase in research regarding the gut microbiome and the implications it has on human health. Not only does it appear to have an effect on weight, heart health and one’s immune system but recent studies have shown that one’s microbiota plays a role in mental health as well. It is believed that the microbiome can have an impact on stress levels, quality of sleep and cortisol release.  In the context of celiac disease, the story of the gut microbiome is that of the chicken or the egg. Does a genetic predisposition for CD result in an affected microbiome or does the microbiome affect risk of CD manifesting. Studies involving identical twins, where one is obese and the other not, have shown that differences in the microbiome are not gene related. This may then suggest that one’s microbiome can contribute to an already existing predisposition to CD.

“Epidemiological data suggest that additional environmental factors, such as type of delivery at birth, milk-feeding practices, intestinal infections, and/or use of antibiotics, could also determine CD risk”.

After coming across a review paper on the implications of the gut microbiome on celiac disease, I became very interested in the idea that environmental factors such as type of delivery and feeding method can have an effect on one’s risk of developing CD through the direct effect on the microbiome. This post will focus on a paper entitled ‘Gut Microbiota trajectory in early life may predict development of celiac disease’. This is hot off the press and published only last year (2018)!

Let’s Review: What do we know

We know that CD only develops in those that have a genetic predisposition to the disease. There is a strong association with the HLA-DQ2 and HLA-DQ8 genes. These are expressed on the surfaces of antigen presenting cells (APCs). When gluten is consumed these APC’s recognise gluten peptides and activate T-lymphocytes which subsequently results in the secretion of pro-inflammatory cytokines and activation of cytotoxic T-cells. This response results in tissue damage leading to the multiple symptoms related to CD. These HLA genes, however, do not guarantee development of CD. They are thus necessary but not sufficient for pathogenesis.

“Although non-HLA variants also contribute to CD risk, studies on the heritability of CD in twins indicate that genetics alone cannot explain CD onset and that non-shared environmental elements also contribute.”

Back to the Paper

This study wanted to investigate “whether alterations in the developing intestinal microbiota and immune markers precede CD onset in infants at familial risk of developing the disease”.

They recruited a cohort of healthy newborns that all had a familial risk of developing CD (at least one first relative having CD). They monitored the progression of the microbiome during the first 5 years of life. After data collection, they compared those infants that developed CD (10 infants) to 10 best-matched controls (regarding type of delivery, HLA-DQ genotype and type of feeding) who did not develop CD by the time the cases did. Their analyses involved DNA typing for the HLA DQ genes, faecal sampling and 16S rRNA sequencing.

Findings

The majority of those infants that developed CD, were diagnosed between 16 and 40 months. At the time of diagnosis, all the CD children had elevated tTG antibody levels. Five presented with symptoms (diarrhoea, abdominal distention, constipation, asthenia) while five had no symptoms.

Although the composition and diversity of the microbiota were not very different between the two groups at six months, it seems that the most significant differences between the CD and control group occurred at 4 months of age. The phylum Firmicutes, for example, had significantly higher relative abundance at 4 months in those children that developed CD compared to those that didn’t. The healthy children, however, had a statistically significant increase in Firmicutes between 4 and 6 months while the CD children started with a high basal level at 4 months and then had relatively constant levels thereafter. This meant that at 6 months there were no differences at the phyla level between the two groups but the developmental process had differed. This pattern was similar in the establishment of Enterococcaceae and Peptostreptococcaceae populations. Levels of intestinal IL-6 were also similar between the groups at 6 months despite the CD group having higher levels at 4 months. It is thus the initial establishment of the bacterial communities that may have an impact on the likelihood of CD development

FYI

tTG antibody: tissue transglutaminase antibody – only made in people with CD
IL-6: pro-inflammatory cytokine

The important take-way message of this paper is the fact that a timely progressive increase in microbial diversity is an important factor in the development of a healthy gut flora. The group that developed CD thus underwent ‘premature maturation’ as a result of higher basal diversity levels. The differences in the developmental pattern of the two groups could be a lead as to why they developed CD. Although this particular paper did not come to any major conclusions and was limited in case and control numbers, it serves as a springboard off which further, more in-depth studies can base their research.

Still not convinced that celiac disease is worth the research? I’ll leave you with some scintillating stats!

  • An estimated 1 in 133 Americans, or about 1% of the population, has celiac disease.
  • It is estimated that 83% of Americans who have celiac disease are undiagnosed or misdiagnosed with other conditions.
  • 6-10 years is the average time a person waits to be correctly diagnosed. (Source: Daniel Leffler, MD, MS, The Celiac Center at Beth Israel Deaconness Medical Center)

Resources

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2 thoughts on “The Mighty Microbiome

  1. Another interesting read! 🙂

    So if an altered microbiome is implicated in increasing one’s risk to CD, given that one has the genetic predisposition, surely treatment with probiotics would be a possible preventative measure?

    Also, what makes some gut microbes bad and others good? Is it due to the presence of distinct antigens which may induce an anti-inflammatory or a pro-inflammatory response? If it was based on the antigens, would that not mean that some individuals might respond differently to the microbes compared to others? Based on how competent their immune system is to detect the microbe?

    Like

    • Thanks Kirsten.
      Research into a relationship between the gut microbiome and CD is in its infancy. Certainly it is not yet known if the difference in microbiome of these infants is due to the genetic predisposition to CD or plays a role in promoting clinical manifestation of CD (the chicken or the egg problem!)
      It is extremely unlikely that probiotics would have an impact on prevention or treatment of CD. It has, however been suggested that faecal transplants may be useful in treating symptoms in people with severe CD that is not controlled by a strict gluten free diet.
      What makes some gut microbes bad and some good? A very complex question to answer. What is interesting is that some good or harmless microbes may become bad (make a person sick) given a certain set of circumstances. This is what makes our field so interesting!

      Like

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