**9. Clinical study design to assess gut microbiome in obesity**

Well-designed clinical studies are urgently needed to better understand the interactions between obesity/obesity treatment and gut microbiome.

Several factors affect the quality of weight-loss studies aimed to assess gut microbiome. A well-calculated sample size allowing subgroup analysis is a key factor. Relevant stratification factors (e.g., race, age, gender, BMI, diet, and medications) at randomization will make the study more informative. Any underestimation of these stratification factors, as it has been the case in several clinical studies, especially in relation to diet and medications, may lead to misleading and conflicting results. The duration of the clinical studies has to be sufficient to allow both short-term and long-term/follow-up assessments. Adequate adjustments should be made during the statistical analysis.

### **10. Ideal gut microbiome**

An ideal gut microbiome should have high diversity. At the level of phyla, the ideal gut microbiome should have low Firmicutes phylum and high Bacteroidetes phylum with a Firmicutes-to-Bacteroidetes phyla ratio < 1.0. At the level of genera, the ideal gut microbiome should be rich in *Prevotella* genus.

The recommended diet to reach the above objectives is a diet adequate in calories (adjusted to the activity), low in fat (< 20% of total macronutrients), and rich in fiber (≥ 30 g/day).

#### **11. Conclusions**

Gut microbiome influences normal physiology and susceptibility to diseases. Profound changes affecting the diversity and the abundance of gut microbiome are associated with obesity. A decrease in microbiome diversity and an increase in the ratio of Firmicutes-to-Bacteroidetes phyla have been reported in obese subjects.

Gut microbiome can be manipulated to change the host metabolism and manage obesity. Potential interventions include diet, prebiotics, probiotics, synbiotics, bariatric surgery, and fecal microbiota transplantation.

A better understanding of the interactions between different diets and gut microbiome should help the development of new guidelines for feeding humans to prevent or manage obesity.

#### **Conflict of interest**

The author received honorarium for consultancy from Gelesis, Inc.

*Weight Management*
