Why test the microbiome more than once?

Unlike human genetic information, our microbial genetic information constantly changes as our gut microbiome responds to changes in our diet, lifestyle, drug use, health status, and travel. Dietary changes,  especially those involving certain fats, animal products, prebiotics, and probiotics [1], can alter intestinal flora within 24 hours of ingestion. Certain medications affect microbiome composition as well, and these changes can correspond to the success rate of these drugs.

Thus, knowledge gained from a series of microbiome samples taken at intervals can offer valuable insights for patients undergoing a dietary, lifestyle, or medical change; experiencing ongoing and unresolved gut issues; or who have recently been hospitalized or diagnosed with a new condition. Because of its usefulness in monitoring and assessing health, repeat microbiome testing may become a standard-of-care monitoring tool in the near future. [2-4]

For patients undergoing treatment, the peer-reviewed literature increasingly shows that the composition of a patient’s microbiome can reflect their drug response. As a result, a time-series analysis of a patient’s microbiome before and during treatment may offer additional insights that, until recently, were not available to healthcare providers. Microbiome analysis can be an additional tool to follow treatment success, similar to parameters such as lipid or blood panels.

Beyond its usefulness to doctors and patients, longitudinal studies of the gut microbiome are increasingly a part of ongoing clinical trials at institutions such as Stanford, Boston Children’s, MD Anderson, USC, Georgetown, and Harvard. In a research setting, the frequency of gut microbiome testing depends on a number of factors: type of intervention (if applicable), budget, condition or disease being investigated (if applicable), and level of subject compliance or patient engagement. Recent longitudinal studies that include gut microbiome testing usually test subjects every one week to one month. [7-12] Offering and studying serial testing are some of the many ways in which uBiome is committed to working with medical providers and researchers to find the most effective way of testing the microbiome.  

 

The effect of dietary changes and probiotics on the microbiome

Below is a sampling of scientific publications showing how dietary changes or probiotic supplementation can influence the gut microbiome. In several of these studies, responses to supplementation varied between patients, suggesting that regular microbiome testing can help a patient determine which intervention works best for them.

 

Dietary Changes:

  • Whole-grain wheat breakfast cereal has a prebiotic effect on the human gut microbiota: a double-blind, placebo-controlled, crossover study [13]

This study compared the impact of Whole Grain (WG) wheat or Whole Bran (WB) consumption on the composition of the microbiota and metabolic activity. WG consumption via breakfast cereal increased Bifidobacterium species in stool samples compared with WB.

  • Determination of the in vivo prebiotic potential of a maize-based whole grain breakfast cereal: a human feeding study [14]

This study focused on the prebiotic effect of Whole Grain (WG) consumption on gut microbiota and colonic metabolic activity. Compared with controls, WG consumption increased the amount of Bifidobacterium species in stool samples. No differences in Short Chain Fatty Acids (SCFA), bowel habit data, and fasted lipids/glucose were found between treatment and control groups.

  • Linking Long-Term Dietary Patterns with Gut Microbial Enterotypes [15]

This study aimed to establish the effect of metformin on the composition and function of gut microbiota in individuals with type 2 diabetes. Results showed that metformin, an anti-diabetes drug, promoted the growth of Bifidobacterium adolescentis, Escherichia, and Intestinibacter. Targeted analysis showed an increase in Akkermansia muciniphilia. Metformin promoted consistent shifts in microbial functions, including increased LPS biosynthesis and SCFA metabolism (butyrate and propionate in men).

  • Artificial sweeteners induce glucose intolerance by altering the gut microbiota [16]

The study analyzed the effects of non-caloric artificial sweeteners (NAS) on gut microbiota and glucose metabolism in a mice model. NAS consumption by mice increased the development of glucose intolerance, microbial dysbiosis, and levels of the SCFAs propionate and acetate. Analysis in humans showed a positive correlation between NAS intake and glucose intolerance.

  • The role of diet on intestinal microbiota metabolism: Downstream impacts on host immune function and health, and therapeutic implications [17]

This review of the relationship between diet and microbiota focused on their effects on immune function and disease pathogenesis. Major conclusions from reviewed literature include the clear influence of diet in microbial diversity, the correlation between microbial gene diversity and metabolic parameters, the role of bacterial SCFA producers on gut immune regulation, and the relationship between TMAO bacterial producers and cardiovascular diseases.

  • Diets that differ in their FODMAP content alter the colonic luminal microenvironment [18]

Researchers compared the effects of a low FODMAP (Fermentable Oligosaccharides, Disaccharides, Monosaccharides, and Polyols) diet on colonic health and fecal microbiota. Results showed differences in absolute and relative bacterial abundance and diversity. However, neither SCFA nor whole gut transit time were observed.

  • Randomised clinical trial: gut microbiome biomarkers are associated with clinical response to a low FODMAP diet in children with the irritable bowel syndrome [19]

The aim of this study was to establish the effectiveness of a low FODMAP diet in decreasing abdominal pain and altering the gut microbiota in children with IBS. Results show that children eating a low FODMAP diet experience a decrease in the severity and number of abdominal pain episodes compared to controls. Although no changes in diversity were detected among groups, some bacterial groups were enriched in subjects on a low FODMAP diet, especially microorganisms linked to FODMAP carbohydrate metabolism.

  • The influence of a short-term gluten-free diet on the human gut microbiome [20]

This study aimed to explore changes in gut microbiota linked to the intake of a gluten free diet (GFD), as well as its effect on gut health. Researchers described moderate changes in microbial composition and diversity. Biomarkers of gut health did not show significant associations with the diet change.

  • Consistent Prebiotic Effect on Gut Microbiota With Altered FODMAP Intake in Patients with Crohn’s Disease: A Randomised, Controlled Cross-Over Trial of Well-Defined Diets [21]

Researchers addressed the effects of varying FODMAP diet content on fecal microbiota and biomarkers of colonic health in Australian patients with Crohn’s disease. The study did not detect differences across diets in fecal pH, amounts of total SCFA, or the amount of individual SCFA. Changes in microbiota composition were modest, though Crohn’s disease symptoms were significantly lower if patients followed a low FODMAP diet compared to a typical Australian diet.

  • Variable responses of human microbiomes to dietary supplementation with resistant starch [22]

In this report, researchers assessed the impact of dietary supplementation with resistant starch on SCFA concentration and the composition of the gut microbiota. Findings report that starch supplementation increased fecal concentration of butyrate – though not propionate – and altered the composition of the microbiota.

  • Health benefit of vegetable/fruit juice-based diet: Role of microbiome [23]

Here, researchers studied whether consuming fruit and vegetable juices modifies intestinal microbiota. Results showed a decrease in the abundance of the phylum Firmicutes, and an increase in Bacteroidetes. Additionally, juice consumption was associated with an increase in plasma, urine nitric oxide, and weight loss.

  • Bread Affects Clinical Parameters and Induces Gut Microbiome-Associated Personal Glycemic Responses [24]

Researchers addressed industrial white or artisanal sourdough bread consumption and its effects on clinical and disease markers and on the composition and function of the gut microbiome. Authors found no significant difference in clinical effects, with gut microbiome composition remaining generally stable. Glycemic response to bread type was person-specific and microbiome-associated, highlighting the importance of personalized nutrition guidance.

 

Probiotics:

  • Rectal administration of Lactobacillus casei DG modifies flora composition and toll-like receptor expression in colonic mucosa of patients with mild ulcerative colitis [25]

This study analyzed the effect of Lactobacillus casei DG (probiotic) on colon microbiota, mucosal cytokine balance, and toll-like receptor (TLR) expression in patients diagnosed with ulcerative colitis. L. casei DG significantly modified the composition of microbial flora associated with the colonic epithelium and induced downregulation of colonic TLR4.

  • Disrupted Intestinal Microbiota and Intestinal Inflammation in Children with Cystic Fibrosis and Its Restoration with Lactobacillus GG: A Randomised Clinical Trial [26]

Researchers  studied the composition of gut microbiota in children with Cystic Fibrosis and its correlation with microbial balance and intestinal inflammation. Results showed a reduction in the richness of CF microbiota and increased intestinal inflammation. When researchers tested the effect of Lactobacillus GG on intestinal microflora and inflammation, they discovered that LGG administration reduced intestinal inflammation.

  • Randomised clinical trial: Lactobacillus GG modulates gut microbiome, metabolome and endotoxemia in patients with cirrhosis [27]

This study showed the safety of Lactobacillus GG administration in patients with cirrhosis and minimal hepatic encephalopathy (MHE). Researchers did not find significant changes in microbial diversity. They also reported a decrease in TNF-𝛼 levels in treated patients.

 

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