What is Your GUT Really Telling You?

A simple fecal sample may be able to predict your patient’s risk for developing type 2 diabetes.  That’s right, not a blood test, but a STOOL test.   Our microbiome, the ecological community of microorganisms that share our bodies, influence our risk for disease.  And not just irritable bowel syndrome but many other diseases including type 2 diabetes, depression, cancer, asthma, psoriasis, and autism.¹  Research regarding the connections between our microbiome and disease has the potential to revolutionize the way we screen, diagnosis, and treat our patients.  This is cutting edge science that every ambulatory care practitioner should pay attention.

The human gut is home to trillions of microorganisms and plays a crucial role in the defense against pathogens and the degradation of non-digestible carbohydrates.²  The microbiome also affects nutrient acquisition, energy harvest, and many metabolic pathways.³  Thus, our microbiome may play a key role in the development of obesity.  This is not a far fetch idea.  Animal studies have shown that when the intestinal bacteria of obese mice are transplanted into gnotobiotic (or germ-free) mice they gain twice as much weight as gnotobiotic mice who receive intestinal bacteria from lean mice donors.⁴

True – the findings from gnotobiotic mice might not be generalizable to humans.  But two recently studies published in the journal Nature provide some evidence that appear to confirm an association between our gut bacteria and metabolic derangements.^5,6  In the first study⁵, fecal samples from 292 Dannish lean (n = 123) and obese (n = 169) volunteers who did not have diabetes were examined using a process called quantitative metagenomics.  In summary:

1. Fecal samples were analyzed to determine the number of microbial genes present.  Individuals were categorized has having either a low gene count (LCG < 480,000 genes) or a high gene count (HGC > 480,000 genes).
2. Differences in the microbial gene composition of the two groups were classified.
3. Phenotypic characteristics (such as insulin resistance, dyslipidemia, and inflammatory markers) of the LGC and HGC groups were compared.

Sixty eight individuals had a LGC and 224 had a HGC.  The stool samples from both groups contained bacterial specifies in different proportions; for example, at the phylum level, Bacteroidetes were more prevalent in LGC individuals whereas Actinobacteria were more prevalent in HGC individuals.  Individuals with a LGC had higher serum leptin and insulin concentrations, greater insulin resistance, and increased serum triglycerides and free fatty acids concentrations (Table 1).  Moreover, LGC subjects had higher serum levels of highly sensitive C-reactive protein (hsCRP) than HGC individuals.  These findings suggest that bacterial richness may identify individuals at an increased risk of adiposity-related disorders and the subsequent development of type 2 diabetes.

Table 1: Phenotypic characteristics based on LGC vs. HGC

*Data reported as median values, interquartile range; p-values adjusted for age and sex

A second study⁶ set out to investigate the impact of a dietary intervention on the gut microbiome.  To accomplish this, 49 obese and overweight French subjects adopted an energy restricted high-protein diet for 6 weeks followed by a 6-week weight-maintenance diet.  Fecal samples were analyzed to determine whether the subjects had a LGC (n = 18) or HGC (n = 27).  At baseline, the LGC group had greater insulin resistance and higher fasting triglycerides as compared to the HGC group.  While the LGC group also had higher LDL cholesterol and hs-CRP concentrations than the HGC group at the beginning of the study, the differences were not statistically significant.  Not surprisingly, the LGC group consumed less fruits, vegetables, and fish prior to study entry than their HGC counterparts. 

After consuming the energy-restricted diet, the gene richness significantly increased in the LGC group (p<0.01).  During the maintenance phase, while there was a slight decline in gene richness in the LGC group, it remained much higher at the end of the 12 weeks when compared to baseline (p<0.01).  In the HGC group, there was no significant change in gene richness or diversity over the course of the 12 week study.  Increases in gene richness were significantly associated with decreases in total fat mass (p=0.032), hip circumference (p=0.01), total cholesterol (p=0.001), and LDL cholesterol (p=0.002).  Increases in gene richness were also accompanied by decreases in serum insulin, insulin resistance, and hs-CRP, but the changes were not statistically significant.  The authors concluded that correcting microbial richness may result in improvements in metabolic derangements.

While both studies identified individuals with a LCG gut microbiome and found that a LGC was associated with several metabolic derangements, many questions remain unanswered.  Are there specific bacteria that are needed for optimal health or is it the richness or general composition of the microbiome that’s important?  While Bacteroidetes has been associated with obesity in some studies⁵, other studies have not shown this association.⁷  Perhaps it’s the richness of our microbiome that’s critical.  With over a trillion microorganisms in our gut, many of the gene clusters (e.g. the proportion of various microbes and the resultant gene composition) have not yet been mapped.  Moreover, not all LGC individuals are obese, and some obese individuals have high gene richness, indicating that our microbiome is but one (of many) factors that influences weight gain. The big question – can we change our microbiome to a healthier pattern and will this change our risk for disease?  Are new drug or probiotic therapies that target our microbiome the way to go?  What do you think?