By Natasha Kisseroudis
What is the gut microbiome?
The gut microbiome consists of all microorganisms that are present in the gastrointestinal tract (GIT). The gut microbiota, more specifically, consists of all bacteria, both commensal and pathogenic that reside in the GI tract. It has gained increasing popularity due to its newly discovered important role in metabolism and immune protection against pathogens (Cresci and Bawden, 2015).
Role of the gut microbiome in disease onset and progression
Increasing evidence is being gathered showing the influence of gut microbiome composition on the onset and progression of chronic, non-communicable diseases such as chronic kidney disease and diabetes (Noce et al., 2019). Moreover, differences in the gut microbiota between individuals have been implicated to influence the onset of obesity. Specifically, studies have shown that genetically lean mice have different microbiome composition to genetically obese mice, that is genetically richer in bacteria responsible for the degradation of polysaccharides (Ley et al., 2005). Transplantation studies on germ-free mice colonised by either microbiota from obese or lean mice showed that the mice receiving obese gut microbiota possesed a higher energy harvesting capacity and showed a greater body fat increase than those receiving lean mice microbiota (Turnbaugh et al., 2006). Additionally the gut microbiome can has strong ties to the rest of the body, for example the brain, through the gut-brain communication axis. Specifically, the gut-brain axis is a bi-directioncal communication pathway that allows information exchange between the gut microbiota and brain through neuro-immuno-endocrine mediators. The gut microbiota have been implicated to play a role in the onset of dementia due to the change in microbiome environment brought about by aging, that affects the central nervous system through the gut-brain axis (Kesika, Suganthy, Sivamaruthi and Chaiyasut, 2021). Therefore, the composition of the gut microbiome is essential to overall health. However, a study conducted by Groussin et al. (year), illustrated that the composition of the gut microbiome is varying and differs between industrial and rural populations due to different rates of horizontal gene transfer within the microbiome (Offord, 2021).
The studies on the role of industralisation on gut microbiome composition
Horizontal gene transfer (HGT) is the exchange of genetic material between organisms without a need for reproduction. It happens through the process of various mechanisms (conjugation, transformation and transduction (Cafini, Romero and Morikawa, 2021)) and is responsible for the spread of antibiotic resistance in bacteria (Burmeister, 2015). Studies analysing bacterial DNA have found that the gut microbiota in individuals living in industrial, urban societies undergo HGT more frequently than the gut microbiota of people living in less developed and more rural areas. An example of a study like this was conducted by Groussin et al. in 2021 and published in The Cell.
Aims: To investigate the rate and HGT patterns within the bacterial genomes of cohorts coming from populations that are industrialised to varying degrees (Groussin et al., 2021).
Method: Groussin and his team sequenced 4,149 microbiomes which they had previously cultured and isolated from the stool samples of 37 individuals coming from 14 populations of different industrialisation levels. These samples were combined with microbiome samples from 11 urban American donors whose microbiome data was filed in the Broad Institute-OpenBiome Microbiome Library (BIO-ML) genome collection, making a total sample size of 48 individuals and a dataset of 7,781 isolate genomes. These individuals were classified as either “rural” or “urban” based on their local population density (SEDAC Population Estimation Service, 2015) and “industrialised” or “non-industrialised” based on the Human Development Index [HDI] at the country level (United Nations Development Program, 2020). The 4 categories of cohort lifestyles generated were: urban nonindustrialised, rural nonindustrialized, urban industrialized and rural industrialized. Genomes were categorised based on genomic similarity which identified 339 bacterial species across 6 phyla.
Results showed that, in general, the gut microbiomes of industrialised individuals undergo HGT more frequently than non-industrialised individuals (Groussin et al., 2021). Another observation was that the gut microbiome tend to undergo horizontal gene transfer in accordance with changes in the host’s lifestyle. Specifically, Groussin’s study showed a significant increase in horizontal gene transfer of antibiotic resistance genes in the guts of Datoga people living in rural Tanzania. Specifically, the exchange of many antibiotic resistance genes related to the metabolism of tetracycline was observed in the Datoga people’s microbiome. This is likely linked to a choice of Datoga people to use tetracycline as their newly introduced livestock antibiotic (Groussin et al., 2021).
Further evidence that the human microbiome changes to suit its host’s lifestyle was provided by the observed regular transfer of genes involved in carbohydrate metabolism within the microbiomes of non-industrialised individuals. This may be linked to the high carbohydrate diet of non-industrialised societies, which mainly consists of fresh fruit and vegetables. Another finding was an increased bacterial virulence exchange within the microbiomes of individuals in industrialized societies as opposed to the microbiome data collected from people in non-industrialised societies. Therefore, the researchers concluded that the functions of horizontally transferred genes within the gut microbiome are a reflection of the host’s lifestyle (Groussin et al., 2021).
Implications and discussion of findings in Groussin’s study
Increased HGT frequencies of the inhabitants of more industrialised societies could be explained by their charactaristic gut microbiome composition which is of relatively low diversity. Further evidence of this observation was provided by a study conducted by Vangay et al. (2018). It was found that the gut microbiome diversity of the examined Southeast Asian migrants decreased within a year of arrival, which may be linked to unfavourable health related consequences observed in these individuals (Vangay et al., 2018). However, despite this widely observed difference in the human gut microbial diversity between different societies, no clear scientific explanation for why bacteria tend to increase their genetic exchange rates in urban societies has been provided. It is possible that HGT is favoured by certain aspects of the industrialised lifestyle. One must consider the changes in the digestive tract microenvironment caused by the differences in diet and exercise of individuals living in industrialised areas compared to inhabitants of non-industrialised areas (Offord, 2021). Specifically, the increased amount of processed food and antibiotics consumed by people living in industrialised areas is believed to significantly reduce the diversity of the gut microbiome (Sonnenburg and Sonnenburg, 2019).
Another important difference between industialised and non-industrialised lifestyles which plays a significant role in shaping the gut microbiome is the higher frequency of cesarean section (Sonnenburg and Sonnenburg, 2019). Specifically, cesarean section decreases the variability of the gut microbiome because when babies are delivered vaginally, they are exposed to and acquire the maternal vaginal and gut microbiota, known as the initial microbiota, which consists mainly of Lactobacillus and constitutes more than half of the total microbiota (Dominguez-Bello et al., 2010). Afterwards, babies acquire their secondary microbiota from their family members and surrounding environment. However, cesarean section-delivered babies initially acquire bacteria only from their surrounding environment, that is bacteria present on the skin of the hospital staff the babies have initial contact with (Dominguez-Bello et al., 2010). Many studies suggest a relationship between cesarean section and autoimmune diseases, but evidence has been inconclusive (Iizumi, Battaglia, Ruiz and Perez Perez, 2017).
On the other hand, a strong correlation has been established between antibiotic exposure and autoimmune diseases. Specifically, an increase has been observed in the amount of children being diagnosed with asthma, especially in industrialised developed countries where antibiotics have been used in livestock for the longest time (Iizumi, Battaglia, Ruiz and Perez, 2017). Moreover a correlation has been found in animal studies between antibiotic use and weight growth, proposing that antibiotics may alter the gut microbiome in such a way that promotes obesity (Iizumi, Battaglia, Ruiz and Perez, 2017). For example, antibiotics are believed to alter the ratio of Firmicutes to Bacteroides, classed as the “obesity index”, which is associated with weight gain (Ridaura et al., 2013).
In conclusion, the composition of an individual’s gut microbiome is significant to their health. However this composition is ever changing in relation to various factors such as age and geographical location. Specifically, as explained above, Groussin’s study found that inhabitants of industrialised societies have a less diverse gut microbiome composition than people living in non-industrialised rural areas. This is due to an increased frequency of horizontal gene transfer occurring in industrialised areas which is potentially brought about by the different lifestyle factors that come with an industrialised lifestyle such as more antibiotics present in livestock, processed food, reduced physical activity and cesarean section. Therefore industrialisation and animal domestication has impacted the gut microbiome by increasing the frequency of horizontal gene transfer (through means such as the introduction of antibiotics into livestock), which has in turn decreased the diversity of the gut microbiome. This limited diversity results in adverse health risks associated with metabolic disorders or chronic diseases.
1. Burmeister, A., 2015. Horizontal Gene Transfer: Figure 1. Evolution, Medicine, and Public Health, 2015(1), pp.193-194.
2. Cafini, F., Romero, V. and Morikawa, K., 2021. Mechanisms of Horizontal Gene Transfer.
3. Cresci, G. and Bawden, E., 2015. Gut Microbiome. Nutrition in Clinical Practice, 30(6), pp.734-746.
4. Dominguez-Bello, M., Costello, E., Contreras, M., Magris, M., Hidalgo, G., Fierer, N. and Knight, R., 2010. Delivery mode shapes the acquisition and structure of the initial microbiota across multiple body habitats in newborns. Proceedings of the National Academy of Sciences, 107(26), pp.11971-11975.
5. Groussin, M., Poyet, M., Sistiaga, A., Kearney, S., Moniz, K., Noel, M., Hooker, J., Gibbons, S., Segurel, L., Froment, A., Mohamed, R., Fezeu, A., Juimo, V., Lafosse, S., Tabe, F., Girard, C., Iqaluk, D., Nguyen, L., Shapiro, B., Lehtimäki, J., Ruokolainen, L., Kettunen, P., Vatanen, T., Sigwazi, S., Mabulla, A., Domínguez-Rodrigo, M., Nartey, Y., Agyei-Nkansah, A., Duah, A., Awuku, Y., Valles, K., Asibey, S., Afihene, M., Roberts, L., Plymoth, A., Onyekwere, C., Summons, R., Xavier, R. and Alm, E., 2021. Elevated rates of horizontal gene transfer in the industrialized human microbiome. Cell, 184(8), pp.2053-2067.e18.
6. Iizumi, T., Battaglia, T., Ruiz, V. and Perez Perez, G., 2017. Gut Microbiome and Antibiotics. Archives of Medical Research, 48(8), pp.727-734.
7. Kesika, P., Suganthy, N., Sivamaruthi, B. and Chaiyasut, C., 2021. Role of gut-brain axis, gut microbial composition, and probiotic intervention in Alzheimer’s disease. Life Sciences, 264, p.118627.
8. Ley, R., Backhed, F., Turnbaugh, P., Lozupone, C., Knight, R. and Gordon, J., 2005. Obesity alters gut microbial ecology. Proceedings of the National Academy of Sciences, 102(31), pp.11070-11075.
9. Noce, A., Marrone, G., Di Daniele, F., Ottaviani, E., Wilson Jones, G., Bernini, R., Romani, A. and Rovella, V., 2019. Impact of Gut Microbiota Composition on Onset and Progression of Chronic Non-Communicable Diseases. Nutrients, 11(5), p.1073.
10. Offord, C., 2021. Gene Exchange Among Gut Bacteria Is Linked to Industrialization. [online] The Scientist Magazine®. Available at: <https://www.the-scientist.com/news-opinion/Gene-Exchange-Among-Gut-Bacteria-Is-Linked-to-Industrialization-68619?fbclid=IwAR0MZMdmxK6EgC1cES0JLe0xAJG89jKtCZsUakCquABbWRcwuPNJPWHN0W0> [Accessed 8 May 2021].
11. Ridaura, V., Faith, J., Rey, F., Cheng, J., Duncan, A., Kau, A., Griffin, N., Lombard, V., Henrissat, B., Bain, J., Muehlbauer, M., Ilkayeva, O., Semenkovich, C., Funai, K., Hayashi, D., Lyle, B., Martini, M., Ursell, L., Clemente, J., Van Treuren, W., Walters, W., Knight, R., Newgard, C., Heath, A. and Gordon, J., 2013. Gut Microbiota from Twins Discordant for Obesity Modulate Metabolism in Mice. Science, 341(6150), p.1241214.
12. Sonnenburg, J. and Sonnenburg, E., 2019. Vulnerability of the industrialized microbiota. Science, 366(6464), p.eaaw9255.
13. Turnbaugh, P., Ley, R., Mahowald, M., Magrini, V., Mardis, E. and Gordon, J., 2006. An obesity-associated gut microbiome with increased capacity for energy harvest. Nature, 444(7122), pp.1027-1031.
14. Vangay, P., Johnson, A., Ward, T., Al-Ghalith, G., Shields-Cutler, R., Hillmann, B., Lucas, S., Beura, L., Thompson, E., Till, L., Batres, R., Paw, B., Pergament, S., Saenyakul, P., Xiong, M., Kim, A., Kim, G., Masopust, D., Martens, E., Angkurawaranon, C., McGready, R., Kashyap, P., Culhane-Pera, K. and Knights, D., 2018. US Immigration Westernizes the Human Gut Microbiome. Cell, 175(4), pp.962-972.e10.