What is the gut microbiota and how does it affect our health?

Gut microbiota

Gut microbiota is a collection of microorganisms: bacteria, fungi, yeasts, viruses, and protozoa that inhabit our intestines. Microbiota can be found not only in the intestines, but we can also distinguish the microbiota of the skin, vagina or respiratory system. Until now, the word intestinal microflora was often used interchangeably, but this word is currently considered archaic and incorrect. “Flora” suggests belonging to the plant kingdom, to which bacteria were previously classified. Today we know that bacteria have many different features than plants, and hence modern taxonomy places bacteria in a separate kingdom. The microbiota should also not be confused with the term “microbiome”. The gut microbiome is a much broader concept and includes not only the microbiota but also molecules produced by the microbiota, such as metabolites, proteins, lipids and mobile genetic elements such as phages and viruses [1].

Each section of the digestive tract has a different composition and number of microorganisms. The first part of the digestive tract, the oral cavity, is inhabited by a huge amount of bacteria estimated at 108 CFU (colony forming units – a unit used in microbiology, determining the number of bacteria in the tested material using the culture method). In later sections, the development of microorganisms is hindered by the rapid transport of food (in the oesophagus) or unfavourable conditions such as low pH (in the stomach), thus in these sections, we can only find about 101-103 CFU. In the intestine, the number of bacteria increases gradually from 105 CFU in the jejunum to 1012 CFU in the large intestine [2]. The large intestine is the main habitat of the intestinal microbiota and the microbiota in general in the body. Although it was once reported that the total mass of bacteria in the body is about 2 kg, the latest studies estimate that the mass of intestinal microorganisms is about 200 g in a person weighing 70 kg [3]. There are six types of bacteria in the large intestine: Firmicutes, Bacteroidetes, Proteobacteria, Actinobacteria, Fusobacteria and Verrucomicrobia, of which Firmicutes and Bacteroidetes are the most numerous. Most of these bacteria are not cultured using traditional microbiological methods, and very advanced techniques such as next-generation sequencing are needed to evaluate and characterize microbiota. Within the intestinal microbiota, we can distinguish the mycobiota, i.e. the part of the microbiota related to fungi. Among the most studied fungi are those belonging to Candida, Saccharomyces, Malassezia and Cladosporium.

Remember, however, that the exact composition is an individual matter and depends on health and eating habits, which is why comparing microbiota profiles between individuals is very difficult.

We must remember that within our intestine there are millions of microorganisms, both beneficial and pathogenic, which compete with each other for nutrients and for a place to live. Any modifications to the diet, medications or diseases may disturb the balance of the intestinal microbiota, which may harm the functioning of our body.

The importance of microbiota?

The main tasks of gut microbiota are:

• Metabolism of non-degradable and hardly degradable substances derived from food
• Improving the minerals’ absorption
• Support for the regulation of intestinal peristalsis
• Production of short-chain fatty acids, including butyric, acetic, propionic and valeric acids 
• Protection against pathogens 
• Inactivation of external toxins and toxins produced during metabolism 
• Stimulating the immune response 
• Synthesis (production) of vitamins, including vitamin K, B1, B6, B12, folic acid 
• Maintaining the proper functioning of the intestinal barrier

With new scientific reports, we know more and more about the importance of microbiota on the health condition of the human body. Commonly is mentioned about the gut-brain axis, in which biochemical signals, in this case, neurotransmitters produced by the intestinal microbiota, modify the functioning of the central nervous system. Very often we also hear that immunity comes from the intestines. It is estimated that the formation of about 70% of all immune cells is related to the digestive system. Currently, interest in gut microbiota is entering various fields of medicine, not only gastroenterology but also endocrinology, dermatology, psychiatry and even surgery.

Dysbiosis – what is that?

Intestinal dysbiosis is a condition in which the gut microbiota is disturbed. Changes can be qualitative and quantitative. This is caused by an imbalance of microorganisms.

Factors contributing to dysbiosis:

• Pharmacotherapy, including antibiotics, proton pump inhibitors and non-steroidal anti-inflammatory drugs 
• Improper diet 
• Chronic stress 
• Inflammation of the intestines 
• Alcohol abuse 
• Iron and vitamin D deficiencies 
• Age 
• Comorbidities 
• Genetic predisposition 
• Type of birth and breastfeeding

The symptoms of intestinal dysbiosis include typical symptoms from the digestive system, e.g. abdominal pain, bloating, constipation, and diarrhoea. However, given the multifaceted importance of the microbiota, long-term dysbiosis can manifest itself through symptoms such as:

• Decreased immunity and susceptibility to viral infections 
• Low mood and depression 
• Chronic fatigue 
• Increased risk of developing autoimmune diseases

Importantly, intestinal dysbiosis is indicated as a potential factor in the pathogenesis of hypertension, cardiovascular diseases, type II diabetes, obesity and autoimmune diseases such as celiac disease, rheumatoid arthritis and type I diabetes. Dysbiosis is also observed in other disease entities, including inflammatory bowel diseases, depression, atopic dermatitis, Alzheimer’s disease or autism.

The most effective way to determine the state of gut microbiota is to quantify bacteria. Now on the market, there are bacterial genome tests available which are based on next-generation sequencing, which very often include metabolic analysis to better understand which bacteria we are lacking and which metabolic pathways may be impaired.

How to deal with dysbiosis?

To heal from dysbiosis, firstly all the factors that led to this condition should be eliminated. And just as we are unable to change the fact of the disease, we can easily improve the quality of sleep, reduce stress or improve our diet. Alcohol and highly processed products should be eliminated. Gut microorganisms like a diet rich in fibre, prebiotics (inulin, FOS) and fermented products and antioxidant products containing, for example, polyphenols (curcumin, resveratrol), which are found in vegetables and fruits. Recently, phenolic compounds, unsaturated fatty acids and other biologically active compounds have been classified as prebiotics, due to their beneficial effect on intestinal bacteria [4].

It is also worth it for our lifestyle to include physical activity that stimulates intestinal peristalsis and metabolic processes, which will also support the functioning and improve the condition of the intestinal microbiota.

Moreover, probiotic therapy can also be introduced, but the selection of the strain and its dosage should always be consulted with a medical doctor.

What if there are too many bacteria?

In most cases, dysbiosis is associated with a state in which we have too few “good” bacteria in the large intestine or the proportion of individual groups of bacteria is disturbed. Lately, a new type of dysbiosis characterized by overgrowth of intestinal bacteria has been observed more and more often. Small Intestinal Bacterial Overgrowth (SIBO) syndrome is a condition in which there is an abnormal overgrowth of bacteria typical of the colon in the small intestine, which is manifested by abdominal pain, bloating, a feeling of fullness, excessive accumulation of gas or slowing down of intestinal peristalsis. Unlike other types of dysbiosis, SIBO is most often treated with antibiotics to reduce the number of bacteria in the gut. It is also important to introduce a diet that will not stimulate the growth of bacteria. The most commonly used diet is low-FODMAP, i.e. containing small amounts of fermentable oligo-, di- and monosaccharides and polyols. It is also often proposed to switch to a ketogenic diet with the elimination of FODMAPs.

Ketogenic diet and gut microbiota – friends or foes?

Despite many studies focused on the microbiota and the impact of various factors on its functioning, few scientific studies definitively determine the direct impact of the ketogenic diet on the gut microbiota. Since the ketogenic diet comes from neurology, the largest amount of research is carried out with patients with neurodegenerative diseases and on animal models.

A pattern of enrichment in the diversity of gut bacteria has been observed in model studies in etomoxir-treated mice and obese mice. However, when these mice were given a high-fat diet (60% of fat), they showed a decrease in diversity. Therefore, it is believed that the ketogenic diet can reduce the diversity of the gut microbiota, which may attenuate the progression of neurodegenerative diseases or obesity [5].

In another study in healthy mice, the ketogenic diet had a positive effect on increasing the number of bacteria considered positive (Akkermansia muciniphila and Lactobacillus) [6].

On the other hand, other studies have shown that the ketogenic diet contributes to intestinal dysbiosis in mice with Alzheimer’s disease [7].

In clinical trials, the ketogenic diet increased the number of Enterobacteriaceae compared to the baseline in a study on people with mild cognitive impairment. Similarly, a decrease in the number of bacteria from the Bifidobacteriacea family also suggested an adverse effect of the ketogenic diet [8]. In addition, in the MS population, a decrease in Akkermansia levels was observed after six months of the ketogenic diet [9], in contrast to the positive increase seen with this bacterium in patients from a previous study [9].

A study conducted in children with epilepsy investigated the relationship between the gut microbiota and seizures. Patients with epilepsy showed an imbalance in the gut microbiota before starting the ketogenic diet. The authors found a greater number of pathogenic proteobacteria (Escherichia, Salmonella and Vibrio), which significantly decreased after treatment with the diet, and an increase in Bacterioidetes in both healthy and children with epilepsy after the keto diet [10]. Researchers suggest that the ketogenic diet may reduce neurological symptoms exactly through changes in microbiota diversity.

There is a lack of research on the impact of a ketogenic diet in a healthy population, thus it is difficult to conclude clearly whether the ketogenic diet has a beneficial effect on our microbiota. I hope that the coming years will bring answers to these bothering questions.

Bibliography:

[1] Berg, G., Rybakova, D., Fischer, D. et al. Microbiome definition re-visited: old concepts and new challenges. Microbiome 2020; 8, 103.

[2] Gałęcka M., Basińska A., Bartnicka A. Znaczenie mikrobioty jelitowej w kształtowaniu zdrowia człowieka — implikacje w praktyce lekarza rodzinnego. Forum Medycyny Rodzinnej 2018; 12(2): 50-59.

[3] Sender R, Fuchs S, Milo R. Revised Estimates for the Number of Human and Bacteria Cells in the Body. PLoS Biology 2016; 14(8): e1002533.

[4] Gibson, G.R.; Hutkins, R.; et al. Expert Consensus Document: The International Scientific Association for Probiotics and Prebiotics (ISAPP) Consensus Statement on the Definition and Scope of Prebiotics. Nature Reviews Gastroenterology & Hepatology 2017; 14: 491–502.

[5] Kaviyarasan S, Chung Sia EL, Retinasamy T, Arulsamy A and Shaikh MF. Regulation of gut microbiome by ketogenic diet in neurodegenerative diseases: A molecular crosstalk. Front. Aging Neurosci. 2022; 14: 1015837.

[6] Ma, D., Wang, A.C., Parikh, I. et al. Ketogenic diet enhances neurovascular function with altered gut microbiome in young healthy mice. Scientific Reports 2018; 8: 6670.

[7] Park, S., Zhang, T., Wu, X., and Yi Qiu, J. Ketone production by ketogenic diet and by intermittent fasting has different effects on the gut microbiota and disease progression in an Alzheimer’s disease rat model. J. Clin. Biochem. Nutr. 2020: 67: 188–198

[8] Nagpal, R., Neth, B. J., Wang, S., Craft, S., and Yadav, H. Modified Mediterranean-ketogenic diet modulates gut microbiome and short-chain fatty acids in association with Alzheimer’s disease markers in subjects with mild cognitive impairment. eBioMedicine 2019; 47: 529–542.

[9] Swidsinski, A., Dörffel, Y., Loening-Baucke, V., Gille, C., Göktas, Ö., Reißhauer, A., et al. Reduced mass and diversity of the colonic microbiome in patients with multiple sclerosis and their improvement with ketogenic diet. Front. Microbiol. 2017; 8: 1141.

[10] Arumugam M., Raes J., Pelletier E., Le Paslier D., Yamada T., Mende D.R., Fernandes G.R., Tap J., Bruls T., Batto J.M., et al. Enterotypes of the human gut microbiome. Nature. 2011;473:174–180.