Remember that first time you fell in love? That reassuring feeling of thinking alike, feeling alike, not needing words to know what your partner is thinking. It’s as if you are one. You can’t live without them, and they can’t live without you.

Whilst codependency isn’t exactly the hallmark of a healthy romantic relationship, in the relationship between humans and their microbes, symbiosis is everything.

Over time humans and microbes have coevolved, an ancient symbiotic partnership where bacteria and animals have learnt to converse. They provide signals to us, and we in turn signal back. It’s a vigorous and resilient setup allowing bacteria to interact with us by modulating our metabolism and immune system [1].

In recent times, however, the cohabitation of microbes and humans has been disrupted. The introduction of modern interactions such as antibiotics, cesarean sections and formula feeding has not only changed the way in which humans acquire ancient microbes, but also their composition. According to Dr Martin Blaser’s disappearing microbes hypothesis [2], our microbiota have been dwindling over generations, the consequences of which aren’t looking pretty.

In a healthy body, ancestral microbes talk to body cells. This leads to normal, long-term functioning of the body. However in a perturbed microbiota – as occurs through antibiotic use [3] – the signals from the microbes to body cells are abnormal, impacting childhood development which can lead to negative long-term physiology outcomes such as inflammatory bowel disease (IBD) , irritable bowel syndrome (IBS), obesity and type 2 diabetes, just to name a few.

One of the most pressing health issues in the world today is obesity. Now a global epidemic, obesity perfectly illustrates what can happen when we mess with the symbiotic relationship between us and our microbes

It’s common knowledge in the farming world that giving low doses of antibiotics to livestock results in the promotion of growth. Experiments conducted with STAT (sub-therapeutic antibiotic treatment) mice show that these mice will gain more weight when fed a high fat diet than germ-free mice (mice lacking a microbiota) [4], indicating a connection between the microbiome and weight gain. Whether this translates to humans is still unclear, but observational data showing a correlation between the rise in obesity and increased antibiotic use [5] is food for thought.

The microbes in our gut are also responsible for how we obtain energy from food, absorb nutrients in the intestine, and other vital processes. A change to the composition of the gut microbiota could therefore influence our predisposition to obesity.

Most concerning perhaps is the connection between early disruption of the microbiome and future health outcomes. In the STAT mice studies, the effects on body mass were most pronounced when antibiotics were given earlier in life [6].

In studies with humans it’s been shown that children exposed to antibiotics in the first six months of life exhibited an increased risk of being overweight at seven years of age [7]. Another study found that kids born by c-section had increased fattiness when controlled for all other known variables.

Bacteria acquired at birth and during the first three years of life are crucial to early development in both mice and humans. Conversely, the loss of ancestral bacteria at this age has been shown to have a deleterious effect on future health.

This points to a need to be mindful of the ways in which we might inadvertently disturb our ancient microbiome.

As in any mutualistic relationship, there’s an understanding that you’re living life in tandem: you scratch my back and I’ll scratch yours. When there is a shift in dynamics and one party is no longer looking out for the other, mutual benefits are lost and both lose out. The same is true for you and your microbiome. Loss of diversity means the team is no longer working optimally and the consequences can be profound. So take care of each other, you’re in this together.

Brigid xx

References

[1] Wu, Hsin-Jung, and Eric Wu. “The role of gut microbiota in immune homeostasis and autoimmunity.” Gut Microbes, vol 3(1), 01/01/2012, 2012, pp. 4-14. NCBI, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3337124/.

[2] Blaser, Martin J. Missing Microbes. HarperCollins Publishers, 2014.

[3] Langdon, A., Crook, N. & Dantas, G. The effects of antibiotics on the microbiome throughout development and alternative approaches for therapeutic modulation. Genome Med 8, 39 (2016). https://doi.org/10.1186/s13073-016-0294-z

[4] Schulfer, A.F., Schluter, J., Zhang, Y. et al. The impact of early-life sub-therapeutic antibiotic treatment (STAT) on excessive weight is robust despite transfer of intestinal microbes. ISME J 13, 1280–1292 (2019). https://doi.org/10.1038/s41396-019-0349-4

[5] Srivastava, Archita. “Early and frequent exposure to antibiotics in children and the risk of obesity: systematic review and meta-analysis of observational studies.” F1000Res, vol. 9, 2020, NCBI, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7429923/

[6] Cox, Laura M, and Martin J Blaser. “Antibiotics in early life and obesity.” Nature reviews. Endocrinology vol. 11,3 (2015): 182-90. doi:10.1038/nrendo.2014.210

[7] Ajslev TA, Andersen CS, Gamborg M, Sørensen TIA, Jess T. Childhood overweight after establishment of the gut microbiota: the role of delivery mode, pre-pregnancy weight and early administration of antibiotics. Int J Obes. 2011; 35:522–529