A deeper look into the gut microbiota including short chain fatty acids, obesity and a case study.
Written by Akshaya, Kavya, Haritha
Microbiota and its involvement in the human gut
Short Chain Fatty Acids - butyrate and propionate
Short Chain Fatty Acids (SCFAs) are byproducts of the bacterial metabolism in our gut microbiome. They are important for the health of our gut, as well as our brain and body (1). SCFAs help to boost the activities of the bacteria in our microbiome as they can serve as food and provide many health benefits for our own bodies as well. Different bacteria in our gut have different metabolic abilities. Some have the ability to break down larger compounds, known as primary feeders, whereas others specify their metabolism to smaller molecules, secondary feeders.
Consumption of dietary fibers increases the amount of SCFAs in your body, derived from whole plant foods (1). Dietary fibers are not digested by our digestive tract. Therefore, these serve as the main food source for the bacterial community in the gut. It goes without saying that including fiber-rich content in our diets everyday is vital in sustaining a healthy and enriched gut microbiota. Now that we know the importance of the SCFAs, let’s see what they look like:
Before we delve into specific SCFAs and their functions, it is important to understand overall, what SCFAs are, and how they are created. Short Chain Fatty Acids are created from the plant based foods in the gastrointestinal tract and act as metabolites, which can conserve energy, signal and influence catalytic activities (2). They are a part of saturated aliphatic fatty acids which contain 2 to 5 carbons (4). Butyrate contains 4 carbons, whereas propionate contains 3 carbons. These compounds contain really long chains of carbon and hydrogen atoms attached to a carboxylic acid group. The hydrocarbon chain is non polar and hydrophobic whereas the carboxylic acid end is polar and hydrophilic. SCFAs are mainly made of acetate, propionate, and butyrate. The amounts of each produced vary depending on the diet of the individual.
Let’s discuss a couple of SCFAs and their health benefits:
Butyrate is created by Firmicutes, which you can learn more about on our previous blog post, from anaerobic respiration (1). Butyrate benefits the brain defending against mental health disorders and aiding in better memory and cognition (1). The main role of butyrate is to act as a major energy source for colonocytes, which are cells that line the gut, and are necessary to protect and preserve the lining that separates the intestines from the rest of the body (1). This prevents pathogens from entering the bloodstream but allows vitamins and minerals to pass by. When we do not eat enough fiber-rich material, the production of butyrate, along with other SCFAs will decline. This leads to a decline in the colonocyte population as they have less food to survive on. When the population of colonocytes is in the decline, other bacteria that are more pathogenic to our gut will start to increase in population. These pathogenic bacteria degrade the mucous lining in our gut and can cause inflammation and infections.
Propionate is also created by the breakdown of dietary fiber and contains many benefits. It is created when carbohydrates are broken down by various phyla including Bacteroidetes, which you can learn about from Part 2 of Microbiota. Propionate is known for being able to reduce one’s appetite by releasing hormones (1). This SCFA is also linked with lowering cholesterol levels and reducing storage of fat, as well as containing anti-inflammatory properties which are produced in the gut, but extend to influencing other parts of the body (1).
Why are SFCAs important?
SCFAs in particular can influence various cognitive processes and interactions between the microbiota, gut, and brain (2). What does this imply? SCFAs serve as intermediate molecules that have been shown to have significant effects on the gut-brain connection. Therefore, what we eat can heavily influence our mood, productivity, and overall mental well-being.
Microbiota and obesity
The mice experiment
So we have given you the talk about the benefits of the microbiota and their function. But how do we know all this? We are going to discuss a classic experiment that was conducted to see how our microbiota affects development and host physiology.
In this experiment, mice were used as the model animals. Germ-free mice are bred lacking any exposure to the outside environment. These mice are important for experiments where we want to explore how certain bacteria play a role in the host. Genetically obese mice and lean mice differ in their microbiota composition where the Bacteriodetes population is low and the Firmicutes population is high as compared to that of the lean mice counterparts (5). The microbial genetic component in the obese mice has a mutation for a gene influencing leptin production, which is an important molecule for combating obesity. In order to see if the microbiota composition from the obese and lean mice have significant effects on the host’s physiology, the experimenters took germ-free mice and transplanted the microbiota from both the obese mice and the lean mice. Other variables such as diet and environment were kept constant. Over time, the germ-free mice with the obese microbiota turned obese, whereas the germ-free mice that were transplanted with the lean microbiota appeared lean. Through other analytical methods, it was revealed that the microbial composition of obese mice leads to more energy extraction. This means that the extra energy harvested in the obese mice stores it in the form of fat. This was an important revelation: the composition of the microbiota has a significant effect on the host’s physiology and overall health. It’s also important to take away that diseases such as obesity, can be potentially treated through altering the microbial composition. However, further research must be conducted in order to get a better understanding. The future of treatments for many chronic diseases rely on their association with the gut microbiota. It is an exciting time to be part of microbial research!
Case study
By understanding this information, we can apply it to human studies which reveal the impacts of human behavior and its influence on the gut microbiota. Here we look at a particular study about the change in the gut microbial composition amongst immigrants in the US.
Immigration to the US and how the microbiota changes
Studies have shown that immigrating to the United States has an impact on gut microbiome diversity as well as the increase in chronic diseases and health conditions such as obesity (6). Some ethnic groups have also experienced a four fold increase in obesity over fifteen years (6). The host microbiome is influenced by the host’s immediate as well as long-term diet. Immigration to the United States causes the loss of native gut microbiota. It has been shown that the western Bacteroides strain replaces the native Prevotella strain (6). Immigration to the US also results in the loss of plant fiber degrading enzymes. Additionally, it was found that changes to the microbiome occur within 9 months of living in the US and the longer a person lives in the US, the less diverse their gut microbiome becomes (6). The reasons for this occurrence are not known yet, and further studies need to be conducted.
What kind of diet promotes the best gut health?
Diets containing a large amount of fiber are considered to be good for the gut since they have a low bioavailability (7). Bioavailability is the amount of a substance that enters blood circulation immediately after being introduced into the body. For foods with low bioavailability, the digestive system is actively used to digest food thereby increasing the amount of nutrients extracted from the food, whereas foods with high bioavailability are absorbed directly into the bloodstream and the digestive system is not actively used, thereby decreasing the amount of nutrients extracted from the food. Unrefined foods that have a low bioavailability (meaning a lower proportion of the substance enters blood circulation immediately when introduced into the body, hence needs to be digested actively) also are beneficial, and the bigger the size of the food particle, the lower the bioavailability (7). Interestingly, bioavailability can be lowered by preventing grinding of foods into very small pieces, which thereby reduces calorie intake (7). Cooking vegetables significantly reduces their bioavailability. For example, cooking (heating) tomatoes causes a chemical compound called lycopene to become three times more bioavailable than in raw tomatoes (7). This means that you get energy much faster from these tomatoes after cooking them, but the nutrient value decreases. We mostly want to eat foods that have low bioavailability in order to promote gut health and microbiome diversity.
Example of microbial gene transfer to humans
Interestingly, genes from organisms present in an individual's diet can be transferred to human beings making them able to digest certain foods better. For example, Japanese have a seaweed digesting enzyme that is also present in the marine bacterium Zobellia galactanivorans (8). This microorganism is known to feed on seaweed and has particular genes that code for enzymes that can break down certain carbohydrates in seaweed. These same enzymes are found in Japanese gut microbiota. A possible reason for this happening is by horizontal gene transfer (a method of gene transfer where genes from one organism are transferred to another completely unrelated organism) from the bacterium to humans over time. The presence of these enzymes in the human Japanese gut help them acquire more nutrients from seaweed as compared to North Americans (8).
Next time you have a meal, make sure to feed your microbiota too!
References:
https://atlasbiomed.com/blog/what-are-short-chain-fatty-acids-and-why-should-you-care/
https://www.frontiersin.org/articles/10.3389/fendo.2020.00025/full
https://www.creative-proteomics.com/services/short-chain-fatty-acids-analysis-service.htm
https://www.sciencemag.org/news/2010/04/japanese-guts-are-made-sushi