Gut Microbiome Is Less Diverse in Teens With Obesity and PCOS

Veronica Hackethal, MD

January 29, 2020

Teens with obesity and polycystic ovary syndrome (PCOS) have decreased bacterial diversity and a more "unhealthy" gut microbiome compared to similar-sized teens without PCOS, according to a new study published online January 23 in the Journal of Clinical Endocrinology & Metabolism.

"We have for the first time demonstrated that obese adolescents with PCOS have an altered gut microbiome compared to girls without PCOS with similar body mass index (BMI), activity level, and dietary habits," write Beza Jobira, MD, and colleagues.

Jobira is affiliated with Children's Hospital Colorado, Anschutz Medical Campus, in Aurora. 

Researchers also observed that higher testosterone levels, which are often found in women with PCOS, were linked to decreased bacterial diversity in the gut.

"The unhealthy bacteria [were] related to higher testosterone concentrations and markers of metabolic complications. The gut microbiome may play a role in PCOS and its related metabolic complications, and these changes can be found in teenagers who are early in the course of the condition," senior author Melanie Cree-Green, MD, PhD, also of Children's Hospital Colorado, said in a press release issued by The Endocrine Society.

"Further work is needed to better understand the relationship between androgens and the microbiome, especially as a potentially new avenue for therapy," the authors write.

Do Girls Obesity and PCOS Have Altered Gut Microbiota?

PCOS affects about 6%-18% of women worldwide but is more common among teenagers who are obese and typically starts in adolescence. Individuals affected by the hormonal condition show a range of symptoms, including acne, excess body hair, and irregular periods.

The condition is linked to increased risk for cardiometabolic conditions including type 2 diabetes and cardiovascular disease, as well as nonalcoholic fatty liver disease (NAFLD), infertility, and depression.

"Despite the increased risk of obesity and metabolic syndrome in women with PCOS, there are limited data linking altered gut microbiota to PCOS," the researchers say.

"Our goal was thus to determine if youth with PCOS and obesity have altered composition of gut microbiota compared to equally obese girls with regular menstrual cycles. This information could provide additional directions to improve treatment and prevention of PCOS," they write.

To study the issue, they conducted a prospective, case-control, cross-sectional study that included 58 teens who were obese and sedentary with an average age of 16 years. Participants were from pediatric endocrinology and lifestyle medicine outpatient clinics at the Children's Hospital Colorado.

The teenagers self-reported dietary and physical activity on standardized questionnaires. Laboratory tests included fasting glucose, sex hormone levels, alanine aminotransferase (ALT, a measure of liver function), inflammatory markers, and lipid levels. Researchers analyzed stool samples for bacterial genetic material.

Compared to participants without PCOS (n = 21), teens with PCOS (n = 37) had significantly decreased α-diversity, a measure of bacterial diversity within each individual participant (Shannon diversity, P = .045 and evenness, P = .0052).

"By closely matching our control and PCOS groups for BMI z score, which is a measure that is adjusted for age, as well as having a very similar absolute BMI, we were able to detect differences based on disease status without the confounder of weight," the researchers observe.

Lower Bacteroidetes Linked to a 4.4-Fold Higher Risk of PCOS

The PCOS group also had significantly decreased β-diversity, a comparison of overall bacterial composition between the two groups (P < .001).

Results also showed a higher percentage relative abundance (%RA) of phyla Actinobacteria (P = .027), lower Bacteroidetes (P = .004), and similar Firmicutes and Proteobacteria in the PCOS group compared with the non-PCOS group.

These four types of bacteria make up the majority of the gut microbiome, the researchers explain.

Changes in the relative abundance of these bacteria have been linked to a high-fat, low-fiber diet, as well as conditions associated with PCOS, including obesity, insulin resistance, type 2 diabetes, NAFLD, and inflammation in general. 

In this study, lower Bacteroidetes was linked to a 4.4 increased likelihood of having PCOS.

Laboratory tests also showed that higher testosterone levels were significantly associated with decreased α-diversity (P < .001).

A range of bacteria were linked to markers of metabolic syndrome, such as waist-to-hip ratio, fasting triglycerides, fasting insulin, and insulin sensitivity.

The study had several limitations. Not all lab tests were available for all participants because they came from three different studies with varying study designs. The study was relatively small, took place at a single tertiary care center, and did not include normal weight individuals with PCOS.

The study was supported by grants from the National Institute of Diabetes and Digestive and Kidney Diseases, Doris Duke Foundation, Boettcher Foundation Webb-Waring award, University of Colorado GI and Liver Innate Immune Program, Center for Women's Health Research, and National Institutes of Health/National Center for Advancing Translational Sciences. The authors have reported no relevant financial relationships.

J Clinical Endocrinol & Metabol. Published online January 23, 2020. Abstract

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