Probiotics and the propensity for portliness

The human gut microbiome is a bit like an ant colony. While individual ants are extremely small, their sheer numbers and work ethic can have a profound effect on the local environment. The gut microbiome consists of up to 100 trillion bacterial cells, compared to the 37 trillion that make up the human body^[1]. While these individual bacterial cells are relatively tiny, they too can have a significant effect on their local environment.

The microbiome has attracted increasing attention over the past year, appearing in the ERD multiple times. This review details a recent study that examined how supplementation of our little gut bugs could potentially help prevent fat mass gain during excess caloric consumption.

There is a lot of evidence that suggests people with metabolic disorders^[2], obesity, or diabetes have a different gut microbiome than healthy people. Dietary changes can also have a significant influence on the type and quantity of gut microbes.

Whether or not these associations are causal is not clear. One candidate for the causal link is endotoxin, or bacterial lipopolysaccharide (LPS, shown in Figure 1). Normally, these lipid-sugar linked molecules are found on the surface of specific strains of bacteria (gram-negative) where they contribute to numerous functions, including improving structural integrity and defending against attack. LPS is either shed while the bacteria are alive or upon their death. These molecules are then able to enter through the partially permeable digestive system and elicit a strong immune response. This response is linked to a host of maladies (at least in rodents), including, but not limited to, obesity and insulin resistance.

Figure 1: The structure of endotoxin

Since diet is able to change the gut microbiome, and there is a possible negative interaction between host and gut microbes potentially mediated through endotoxins, it comes as no surprise that diet, particularly high-fat diets, can affect circulating endotoxin concentrations. These elevated endotoxin levels could then lead to an innate immune response that results in low-grade systemic inflammation^[3] and negatively impact glucose homeostasis.

Only specific strains of bacteria are responsible for the production of endotoxins. Theoretically, shifting the gut microbiome away from these strains could ameliorate some of the negative effects attributed to endotoxins. This has been a relatively recent avenue of investigation for scientists, which has demonstrated that specific species compete with gram-negative strains^[4]. This mechanism could help explain the results of some previous reports of probiotic supplementation, which found that these probiotics can regulate weight gain^[5].

This study examines supplementation of probiotics during a high-fat hypercaloric diet. It is different from from past studies in that it has a slightly longer duration (14 days), uses a multi-strain probiotic, and investigates weight gain in healthy individuals. Researchers also made an effort to determine the mechanism of action responsible for any health effects.

The gut microbiome changes in response to diet and is a potential factor in weight gain and insulin resistance. One player that mediates this interaction is a group of compounds found within bacteria called endotoxins, which are able to elicit a strong immune response. These endotoxins are only produced by specific bacteria. The objective of this study was to observe if probiotic supplementation aimed at changing the microbiome to produce fewer endotoxins could modulate weight gain during a hypercaloric diet.