Endocrine Feedback Loop – EFL069

Episode Title: The Gut Microbiome in Type 1 Diabetes and Obesity
Podcast Date: January 15, 2026
Host: Dr. Chase Hendrickson, Vanderbilt University Medical Center
Guests:

• Dr. Ashok Balasubramanyam, Baylor College of Medicine
• Dr. Oka Lernmark, Lund University, Sweden

Episode Overview

This episode reviews key findings from a February 2025 Journal of Clinical Endocrinology and Metabolism article examining gut microbiome differences in adolescents with type 1 diabetes (T1D), comparing those with obesity versus those with normal BMI. The discussion unpacks the study’s design, methods for microbiome analysis, and clinical implications, featuring insights from leaders in T1D research.

Main Discussion Points & Insights

1. Background and Rationale

Timestamps: 02:53 – 12:35

• Rising obesity in T1D: The prevalence of obesity among adolescents with T1D complicates its metabolic profile, introducing additional insulin resistance atop existing insulin deficiency.
• Microbiome in disease: Both T1D and obesity are linked with gut dysbiosis, but it’s unclear how their combination affects the microbiome’s composition and function.
• Landmark studies: The TEDDY study is cited as foundational in mapping the developmental trajectory of the gut microbiome in early life.

Quote:
“Type 1 diabetes is a very complex disease, which means that the environment has an enormous effect on its pathophysiology and natural history.”
— Dr. Ashok Balasubramanyam [02:54]

2. Defining Gut Dysbiosis and Microbiome Development

Timestamps: 06:43 – 11:33

• Individualized microbiome: The gut microbiome matures through distinct phases and stabilizes by age four, with composition shaped by individual and country-specific factors.
• Imbalance as loss and replacement: Dysbiosis may result from loss of beneficial microbes and expansion of less favorable species, often triggered by disruptions like antibiotics.

Quote:
“The developing gut microbiome...undergoes three distinct phases...this, to our surprise, was followed by a stable phase where each individual...acquired the personalized microbiome.”
— Dr. Oka Lernmark [07:46]

3. Study Design and Methodological Considerations

Timestamps: 12:35 – 23:56

• Study structure: Cross-sectional analysis of 48 adolescents (11–19 years) with established T1D, divided into lean (n=27) and obese (n=21) groups; groups matched for age, sex, and race.
• Confounding factors: The study adjusted for common variables but couldn’t account for everything. Noted residual confounders include residual insulin production, medication use, and unmeasured dietary factors.
• Sample exclusions: Only kids with T1D and no recent infection, immunosuppression, glucocorticoid, or metformin use.

Quote:
“You do have to be aware that this is a potential weakness of a cross sectional study...you could potentially flip a cause and effect...”
— Dr. Chase Hendrickson [13:04]

4. Microbiome Analysis Techniques

Timestamps: 19:32 – 23:56

• Modern stool sampling: Descriptions of advances in collection tubes, preservatives, and the now-standard use of next-generation DNA sequencing for bacterial identification.
• Objective vs subjective data: 24-hour dietary recall is subjective; everything else (microbiome profiling, metabolite measurement) is objective.

Quote:
“We had to invent our own collection tubes...This has now become routine. It's very elegant.”
— Dr. Oka Lernmark [19:39]

5. Key Results

Timestamps: 25:14 – 30:58

• Diversity measures:
  • Alpha diversity (within-sample richness/evenness): No difference between groups.
  • Beta diversity (between-group differences): Significant differences observed.
• Microbial patterns:
  • Lean group: Higher Bacteroides abundance.
  • Obese group: Higher Prevotella abundance & higher PB (Prevotella/Bacteroides) ratio—a marker often seen with obesity.
  • Deeper analysis: Obese group had more fermenting bacteria; lean group had more short-chain fatty acid (SCFA) producers.
• Functional pathways:
  • Obese: Enrichment in bacterial pathways synthesizing branched-chain amino acids (BCAAs).
  • Lean: Higher pathways for BCAA degradation.
• Metabolites: Obese group had higher fecal levels of SCFAs (butyrate, acetate, propionate).
• Dietary intake: No significant 24-hour dietary recall differences between groups.

Quote:
“The authors here...are trying all three levels of outcomes: kind of bacteria, what they produce, and pathway analysis.”
— Dr. Ashok Balasubramanyam [25:53]

6. Interpreting the Findings & Clinical Implications

Timestamps: 30:58 – 34:20

• Microbial shifts matter: The increased PB ratio and Prevotella prevalence in obese T1D youth highlights microbiome features associated with obesity, even within a T1D cohort.
• Function not just form: Differences in pathways (e.g., BCAA synthesis/degradation, bile acid biosynthesis) suggest microbiome changes may impact metabolism and risk features.
• Measurement strengths: Use of gas chromatography for SCFA quantification adds robustness to microbiome DNA findings.
• Limitations: Small sample size, cross-sectional design, and subjectivity in dietary data limit causal inference.

Quote:
“It's an important additional observation to their microbiome DNA sequencing.”
— Dr. Oka Lernmark, on SCFA metabolite analysis [33:29]

7. Critical Appraisal and Future Directions

Timestamps: 34:20 – 40:01

• Quality: Strong measurement and analysis techniques for a preliminary study.
• Sample size caveat: Despite being underpowered, some clear differences emerged—signals worth future pursuit.
• Targeted therapy: Mechanistic microbiome insights could pave the way for more tailored intervention strategies in T1D subpopulations, especially focusing on obesity and insulin resistance.
• Genetic context: Discussion of HLA types associated with higher BMI and their potential interplay with microbiome dynamics in T1D children.
• Clinical translation: Identifying and addressing obesity-related microbiome patterns might help reduce complications in T1D.

Quote:
“There are some very interesting observations that should open the door for future studies.”
— Dr. Ashok Balasubramanyam [37:29]

Notable Quotes & Timestamps

• “Type 1 diabetes is a very complex disease, which means that the environment has an enormous effect on its pathophysiology and natural history.”
  – Dr. Ashok Balasubramanyam [02:54]

• “The developing gut microbiome...undergoes three distinct phases...followed by a stable phase where each individual...acquired the personalized microbiome.”
  – Dr. Oka Lernmark [07:46]

• “You do have to be aware that this is a potential weakness of a cross sectional study...you could potentially flip a cause and effect...”
  – Dr. Chase Hendrickson [13:04]

• “We had to invent our own collection tubes...This has now become routine. It's very elegant.”
  – Dr. Oka Lernmark [19:39]

• “It's an important additional observation to their microbiome DNA sequencing.”
  – Dr. Oka Lernmark, on short-chain fatty acid measurements [33:29]

Important Segment Timestamps

• Background on T1D & Gut Microbiome: 02:53 – 06:43
• TEDDY Study & Microbiome Development: 06:43 – 11:33
• Study Design/Methodology: 12:35 – 23:56
• Results—Microbiome Differences: 25:14 – 30:58
• Interpretation & Clinical Implications: 30:58 – 34:20
• Critical Appraisal & Future Directions: 34:20 – 40:01

Conclusion

This episode provided an in-depth review of a small but advanced cross-sectional study evaluating gut microbiome and metabolite differences in obese versus lean adolescents with T1D. While constrained by sample size and inherent methodological challenges, the study’s results reinforce the complexity and clinical relevance of microbial-host interactions in T1D, especially as obesity rates rise in this population. The conversation highlighted the need for further research integrating genetic, metabolic, and microbiome insights to advance personalized management of T1D.