Cell signalling in the gut microbiome
Introduction
Research and interest in the gut microbiome has gained huge momentum over the last 15 years and
our understanding of the role it plays in the body is only really beginning to be understood. The gut
microbiome weights approximately 2kg (a greater mass than the human brain). It is made up of
microorganisms such as bacteria and fungi which vary from person to person but it could have an
impact on a host of physiological functions from mental wellbeing, such as depression and anxiety,
to playing a role in our immune system, to controlling appetite and obesity.
Cell signalling and the microbiome
The microbes in the gut produce thousands of small molecules that can bind to and interact with the
cells in the host. Theses signalling molecules, such as short-chain fatty acids (SCFAs), bile acids and
neutrotransmitters, allow the ‘crosstalk’ between the microbiome and the host. These molecules are
released by the microbes and can affect the host cell in a number of different ways. One of the ways
this occurs is by the molecules binding to receptors such as G-protein-coupled receptors or toll-like
receptors in the cell membrane of the host cells. This then causes a signal transduction and cellular
response to occur. Others can pass through the membrane and cause changes to the mitochondria
that can impact energy release. Other molecules can cause changes in gene expression or epigenetic
changes which can impact on whether a protein is synthesised or not (Zheng et al., 2022). The
possible cell signalling pathways are summarised in the diagram below.
Diagram 1: The cell signalling pathways of the gut microbiome (modified) (Zheng et al., 2022).
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Cell signalling in the gut microbiome
Future implications of studying the microbiome
There are multiple factors that can affect the health of the microbes in the gut as shown in diagram
2. These include out diet (such as fibre intake), drugs (such as antibiotics) and our exercise. If we
change these factors, then we can ‘remodel’ the microbes and change the signalling chemicals that
they give out. This could result in the development of drugs which are targeted to influence
particular aspects of these signalling pathways in order to treat diseases that could be linked to the
chemicals produced by the microbes (Zheng et al., 2022).
Diagram 2: A diagram showing the factors that could influence the gut microbiome and its signalling
pathways(modified) (Zheng et al., 2022).
Professor Tim Spector studied 15,000 twins over 30 years in his TwinsUK study and found that even
genetically identical twins respond to the same foods very differently. He has developed a set of
genetic tools to analyse the gut microbiome and then advise people on the best foods to eat to suit
their individual microbes in order to regulate their weight in a personalised approach. He is also
using this research to investigate how the microbiome is linked with other aspects of health and
diseases in the hope that further research on the chemicals that the bacteria produce may result in
new drugs for treating various diseases such as rheumatoid arthritis (TwinsUK, 2024).
There is even evidence that a faecal transplant (taking the faeces which contains a healthy
microbiome from a donor and placing it into a patient) may help to treat diseases such as Chrohn’s
disease where there is inflammation of the gut (Fehily et al., 2021), although more studies need to
be done first before this becomes a treatment plan.
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Cell signalling in the gut microbiome
Questions
1. Name the ligands mentioned in the article.
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2. Which examples are given of receptors where these ligands may bind?
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3. Suggest why only a specific ligand will bind to a specific receptor.
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4. Outline the outcome of this binding.
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4. Suggest how knowledge of the cell-signalling mechanisms associated with the gut microbiome might be
used to provide personalised weight loss advice to obese people.
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5. Suggest what other information or investigations might be needed to identify whether feacal transplants
could be a successful treatment option for patients with Chrohn’s disease?
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References:
Fehily SR, Basnayake C, Wright EK, Kamm MA. Fecal microbiota transplantation therapy in Crohn's disease:
Systematic review. J Gastroenterol Hepatol. 2021 Oct;36(10):2672-2686. doi: 10.1111/jgh.15598. Epub 2021
Jul 6. PMID: 34169565. Fecal microbiota transplantation therapy in Crohn's disease: Systematic review -
PubMed (nih.gov) [Accessed 29/1/24]
Zheng, Cai & Hao. (2022). Emerging targetome and signalome landscape of gut microbial metabolites, Cell
Metabolism, Volume 34, Issue 1. https://www.sciencedirect.com/science/article/pii/S1550413121006306
[Accessed 29/1/24]
https://twinsuk.ac.uk/ [Accessed 29/1/24]
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