Gut microbiome inputs and outputs

In this article we explore the gut microbiome inputs and outputs, the most well-known of which are dietary fibre (input) and short-chain fatty acids (output).

Composition of the gut microbiome

Generally speaking, it is known which bacterial phyla are the main components of the human gut microbiome (phyla = plural of phylum, the fourth out of nine broadest biological classification – see this graphic for clarity). Of the core phyla, Firmicutes and Bacteroidetes are the most prominent (about 90%) (1).

The composition of the gut microbiome changes in the different sections of the gastrointestinal tract due to changes in pH, oxygen availability, etc.

It has been said that each person’s gut microbiome is as unique as their fingerprints. This is because this microbial composition depends on whether the person was born vaginally or via C section, whether they were fed breast milk or formula, their age, sex, diet, ethnicity, medications, etc. (1).

Manipulating the gut microbiome composition of an individual via various interventions (such as dietary changes, faecal transplants, and antibiotic use) can have effects on metabolic function and weight loss. However, the extent of these effects depend on many individual factors, including age, usual diet, metabolic health (1) and baseline microbiome composition (1, 2).

In addition, it seems that the composition of a person’s gut microbiome is more strongly determined by their usual diet than by transient changes (1, 3). This is yet another argument for focusing on building healthy habits rather than looking for short-lived temporary solutions.

Metabolic health and gut microbiome

Metabolic disorders, which include obesity, insulin resistance (IR) and type 2 diabetes mellitus (T2DM) (1, 2), non-alcoholic fatty liver disease (NAFLD), deranged blood lipids and hypertension (2), are associated with changes in gut microbiome composition as well as decreased numbers and diversity (1, 2).

Gut microbiome inputs and outputs

Inputs

Dietary fibre

Digestible carbohydrates are broken down and absorbed in the small intestine. Dietary fibre and other carbohydrates that escape digestion in the small intestine make their way to the large intestine where they are fermented by bacteria, producing short-chain fatty acids (SCFAs) (1).

The types of fibre that have more impact on the gut microbiome are those which can be more easily fermented, including ß-glucan, inulin and galacto-oligosaccharides. Moreover, different bacteria ferment different fibres and therefore it makes sense to include a variety of fibre-containing foods in the diet (1).

Protein

Most of the protein we eat is digested in the small intestine. A small percentage (around 10%) makes its way into the large intestine, especially in the context of low dietary fibre intake. Both plant- and animal-based proteins can be metabolised in the large intestine, however plant cell walls make the former harder to digest (1).

Unlike SCFAs, most (but not all!) metabolites derived from protein fermentation may have detrimental effects on metabolic health, including trimethylamine (TMA) (1, 2). TMA can be converted from choline and carnitine, which are present in liver, eggs, meat, fish, dairy products and, to a lesser extent, beans, grains, nuts and seeds.

Fatty acids

The available data indicates that a higher saturated fatty acid intake is correlated with lower microbial abundance and diversity in the gut (1).

Polyphenols

Polyphenols are compounds present in plant foods with beneficial properties, such as antioxidant, anti-inflammatory and protective against cardiovascular disease, cancer and other health conditions (1). Dietary polyphenols are absorbed thanks to the action of the gut microbiome (3).

Outputs

Bacterial metabolism generates multiple outputs. Many of these metabolites have been studied due to their ability to affect various aspects of human health, including SCFAs, TMA, amino-acid derived compounds, lipopolysaccharides, and bile acids.

Short-chain fatty acids

As seen before, SCFAs are derived mostly from fibre fermentation (1, 4) but also from certain amino acids and phytate (4). These include butyrate, propionate and acetate (2). In general, SCFAs seem to have positive effects in several aspects of immune and metabolic health (1, 2). More specifically, butyrate and propionate are responsible for gut integrity and immune function, and acetate is used in lipogenesis and gluconeogenesis (3). Succinate plays roles in the Krebs cycle and mitochondrial metabolism, however there are contradictory findings regarding its role in health (4).

Individuals with obesity and diabetes tend to have less bacteria that produce SCFAs and there is some evidence that SCFA administration may produce hormonal changes that lead to weight loss (2).

Trimethylamine

TMA gained a lot of interest a few years ago thanks to media outlets reporting on the detrimental effects of its product trimethylamine N-oxide (TMAO), which is converted in the liver (1, 2). TMAO is associated with cardiovascular disease (1, 2), NAFLD, systemic inflammation, IR, T2DM (1) and kidney failure (2).

Amino-acid derived compounds

These include indole (1, 2), tyramine, tryptamine and SCFAs (1), which can have positive effects on satiety and gut motility (1).

Lipopolysaccharides

Lipopolysaccharides (LPs) are not a product of bacterial metabolism, but rather toxins found in the cell membrane of gram-negative bacteria. When released into circulation (for example, due to compromised gut integrity), they can activate the immune system generating a chronic state of inflammation (4).

Bile acids

Bile acids (BAs) produced in the liver are essential for the digestion and absorption of fats and fat-soluble vitamins. Most of them are reabsorbed in the intestine and recycled in the liver. They can also be converted into secondary BAs by gut microbes or excreted in stools. BAs have also been found to activate receptors leading to other favourable metabolic effects, including increases in insulin sensitivity, satiety and energy expenditure via increased thermogenesis. Secondary BAs may also have a role in the regulation of metabolism and inflammation (2).

References

1. Jardon KM, Canfora EE, Goossens GH, Blaak EE. Dietary macronutrients and the gut microbiome: a precision nutrition approach to improve cardiometabolic health. Gut. 2022 Jun;71(6):1214–26.
2. Agus A, Clément K, Sokol H. Gut microbiota-derived metabolites as central regulators in metabolic disorders. Gut. 2021 Jun;70(6):1174–82.
3. Marchesi JR, Adams DH, Fava F, Hermes GDA, Hirschfield GM, Hold G, et al. The gut microbiota and host health: a new clinical frontier. Gut. 2016 Feb;65(2):330–9.
4. de Vos WM, Tilg H, Van Hul M, Cani PD. Gut microbiome and health: mechanistic insights. Gut. 2022 May;71(5):1020–32.

[Photo by Louis Hansel on Unsplash]