By Julita Baker, PhD

In parts one and two of “Microbiome and Health,” we learned how we acquire the microbes in our gut, why having the right species and diversity is important (remember the “lush” rainforest and “barren” desert example?) and we gave an example of how our gut microbiology influences blood glucose regulation (this is important, as impairment in glucose control is associated with obesity, pre-diabetes, type 2 diabetes, non alcoholic fatty liver disease, and others).  

We now know that having the right microbes is essential to health. But how exactly do we help the “right” strains flourish? What environments should we expose ourselves to? And, what lifestyle factors do we incorporate to integrate healthy strains of bacteria into our gut and get rid of bad ones?

In the next couple of posts, we will discuss how exactly we can do that. How we can flourish optimal strains and promote diversity of microbes to create this “lush” bacterial ecosystem. 

But first, what are these important strains of bacteria, and what does research tell us about their relevance?

Everything you eat modulates the gut microbiota

Before we dive into what we should and shouldn’t eat, let’s take a lesson in the taxonomic rank (I promise, this will be relevant).

In biological classifications, we use this chart to group organisms (remember in grade school when you were taught the “Kings Play Chess On Fine Grain Sand?” Yeah, that classification, which stands for “Kingdom, Phylum, Class, Order, Family, Genus, and Species).

You have more specific descriptions of the life form at each rank. There are 3 domains: Archaea, Bacteria, and Eukarya. Humans are in the domain Eukarya, and our gut friends are in the domain Bacteria. 

As an example, that Lactobacillus acidophilus that you’re eating in your yogurt: Lactobacillus is on the genus level, and acidophilus is a species. But, this Lactobacillus acidophilus is also in the: 

Family: Lactobacillaceae

Order: Bacilli

Phylum: Firmicutes

Domain: Bacteria

How does this taxonomic rank relate to the microbiome and health?

What we see in gut microbiomes, is that more than 90% of sequences of microbes living in our digestive system (1) belong to two Phyla: Bacteroidetes and Firmicutes. 

 The ratio between the two is highly variable and is now proving to be important in health and disease. Its proportion has been noticed to be different in obesity (1, 2, 3, 4), in conditions such as inflammation and metabolism (4, 5, 6) as well as in age (7). 

In a 2006 benchmark study (1) by Microbial Ecologist Jeff Gordon and colleagues, researchers showed that there is a decreased proportion of Firmicutes to Bacteroidetes ratio in people who are lean versus obese, and in people who lose weight. So, 

 Lean = Higher Bacteroidetes

Less Lean = Higher Firmicutes

 In this study, 12 obese individuals were put on either a fat restricted or carbohydrate restricted low calorie diet and their gut microbes were tested over the course of 1 year. 92.6% of the bacterial sequences were from the Bacteroidetes and Firmicutes phyla. Before the two diets began, these 12 people had less Bacteroidetes and more Firmicutes than lean controls. Over time on each diet, the ratio of Bacteroidetes increased and Firmicutes decreased as study subjects lost weight. Researchers also noted an increase in Bacteroidetes correlating with loss in body weight percentage, not with calorie amount over time.  

 What does this tell us?  

 This shows us that losing weight, irrespective of diet type, contributes to a shift in this microbial ratio.

What else do we know about the Bacteroidetes/Firmicutes ratio?

1. We also see more abundance of Bacteroidetes phylum with an increased diversity of the microbiome (nonlinear) (8). In this recent 2020 study published in Nature, researchers found, in 3400 individuals, over 150 dietary and lifestyle factors that influence microbial diversity. Among many factors, they found significant negative associations between BMI, weight, and blood pressure with diversity, while oily fish intake, vigorous physical activity, and vegetable intake (salad and cruciferous vegetables) were positively associated with diversity. (Remember, higher diversity of our gut microbes is typically associated with better health- the lush rainforest versus barren desert example from our last post). 

2. We see that transplanting microbes from a normal mouse into a germ-free mouse increases its body fat without increasing food intake (1). 

3. We see children living in rural areas in Africa (9) having a higher abundance of Bacteroidetes to Firmicutes compared to children in modernized western countries. The main dietary difference there being a high fiber diet compared to a high protein, fat, sugar, starch, diet, respectively. This tells us again, that diet and lifestyle do in fact influence the B/F ratio. 

4. We see that the ratio is highly influenced by environmental changes (10) such as consumption of heavy metals, chlorinated water, food additives, antibiotics, pesticides. So environmental factors matter. 

5. There's definitely more to the story though. Firmicutes produce more Butyrate, which is health-promoting. We see increased insulin sensitivity (12), and anti-inflammatory effects (14), as well as increases in leptin gene expression, the satiety hormone that tells you to stop eating (13).

6. Here is a great review (11) discussing the relevance of the Firmicutes/Bacteroidetes ratio. In it, researchers describe that there might not be a perfect healthy microbiome distribution (only focusing on a higher Bacteroidetes/Firmicutes ratio, for example) but multiple states where we have different sets of beneficial microbes working together that might be the ideal to work towards.  

More in Part IV! 

So we learned about the two main divisions of bacteria that are important to focus on in health. We saw there is a difference in Bacteroidetes to Firmicutes ratio in leanness versus obesity, that the ratio is influenced by what we eat and what lifestyle and environmental factors we expose ourselves to, and we saw that transplantation of microbes from a normal mouse to a germ-free mouse, gives the germ-free mouse the “normal” mouse phenotype, irrespective of amount eaten.

 In the next post, we will delve into what exactly these lifestyle factors and foods we should be consuming to flourish healthy microbes are. Here is a sneak peek :)

References

1. Ley RE, Turnbaugh P, Klein S, Gordon JI: Microbial ecology: human gut microbes associated with obesity. Nature. 2006, 444: 1022-1023. 10.1038/4441022a.

2. Ley, R. E., Backhed, F., Turnbaugh, P., Lozupone, C. A., Knight, R. D., Gordon, J. I. (2005). Obesity alters gut microbial ecology. Proc. Natl. Acad Sc.i U. S. A. 102 (31), 11070–11075. doi: 10.1073/pnas.0504978102

3. Turnbaugh, P. J., Ley, R. E., Mahowald, M. A., Magrini, V., Mardis, E. R., Gordon, J. I. (2006). An obesity-associated gut microbiome with increased capacity for energy harvest. Nature 444 (7122), 1027–1031. doi: 10.1038/nature05414

4. Verdam, F. J., Fuentes, S., de Jonge, C., Zoetendal, E. G., Erbil, R., Greve, J. W., et al. (2013). Human intestinal microbiota composition is associated with local and systemic inflammation in obesity. Obesity (Silver Spring) 21 (12), E607–615. doi: 10.1002/oby.20466

5. Cani, P. D., Possemiers, S., de Wiele, T., Guiot, Y., Everard, A., Rottier, O., et al. (2009). Changes in gut microbiota control inflammation in obese mice through a mechanism involving GLP-2-driven improvement of gut permeability. Gut 58 (8), 1091–1103. doi: 10.1136/gut.2008.165886

6. de La Serre, C. B., Ellis, C. L., Lee, J., Hartman, A. L., Rutledge, J. C., Raybould, H. E. (2010). Propensity to high-fat diet-induced obesity in rats is associated with changes in the gut microbiota and gut inflammation. Am. J. Physiol. Gastrointest. Liver Physiol. 299 (2), G440–448. doi: 10.1152/ajpgi.00098.2010

7. Mariat, D., Firmesse, O., Levenez, F. et al. The Firmicutes/Bacteroidetes ratio of the human microbiota changes with age. BMC Microbiol 9, 123 (2009). https://doi.org/10.1186/1471-2180-9-123

8. Manor, O., Dai, C.L., Kornilov, S.A. et al. Health and disease markers correlate with gut microbiome composition across thousands of people. Nat Commun 11, 5206 (2020). https://doi.org/10.1038/s41467-020-18871-1

9.  De Filippo, C.; Cavalieri, D.; Di Paola, M.; Ramazzotti, M.; Poullet, J.B.; Massart, S.; Collini, S.; Pieraccini, G.; Lionetti, P. Impact of diet in shaping gut microbiota revealed by a comparative study in children from Europe and rural Africa. Proc. Natl. Acad. Sci. USA 2010, 107, 14691–14696

10.  Candela M, Biagi E, Maccaferri S, Turroni S, Brigidi P. Intestinal microbiota is a plastic factor responding to environmental changes. Trends Microbiol. 2012 Aug;20(8):385-91. doi: 10.1016/j.tim.2012.05.003. Epub 2012 Jun 5. PMID: 22672911.

11.  Magne F, Gotteland M, Gauthier L, Zazueta A, Pesoa S, Navarrete P, Balamurugan R. The Firmicutes/Bacteroidetes Ratio: A Relevant Marker of Gut Dysbiosis in Obese Patients? Nutrients. 2020; 12(5):1474. https://doi.org/10.3390/nu12051474

12. Gao, Z.; Yin, J.; Zhang, J.; Ward, R.E.; Martin, R.J.; Lefevre, M.; Cefalu, W.T.; Ye, J. Butyrate improves insulin sensitivity and increases energy expenditure in mice. Diabetes 2009, 58, 1509–1517.

13. Soliman, M.M.; Ahmed, M.M.; Salah-Eldin, A.-E.; Abdel-Aal, A.A.-A. Butyrate regulates leptin expression through different signaling pathways in adipocytes. J. Vet. Sci. 2011, 12, 319–323.

14. Säemann, M.D.; Böhmig, G.A.; Österreicher, C.H.; Burtscher, H.; Parolini, O.; Diakos, C.; Stöckl, J.; Hörl, W.H.; Zlabinger, G.J. Anti-inflammatory effects of sodium butyrate on human monocytes. Potent inhibition of IL-12 and up-regulation of IL-10 production. FASEB J. 2000, 14, 2380–2382.