🧵 8/8
Understanding pathogen–host–microbiome interactions could reshape how we study TB.
Grateful to the colleagues in this international team spanning TB, microbiome, and immunology research. 🙏
🔗 t.ly/jMK3R
Posts by Sergio Serrano-Villar
🧵 7/8
Key unanswered questions:
🔬 Which microbes matter?
🫁 Which metabolites mediate host–microbiome crosstalk?
📉 Are there microbiome-associated biomarkers?
💊 Can we design microbiome-targeted adjunct therapies
🧵 6/8
How could the microbiome influence TB biology? 🧬
Microbial metabolites and dysbiosis may alter immune signaling, affecting inflammation, granuloma stability, and disease progression
🧵 5/8
Moving beyond associations requires integrating multiple data layers.
Combining microbiome data with:
🧬 host transcriptomics
🧪 metabolomics
🧫 immune profiling
can help identify mechanisms linking microbiota and TB biology.
🧵 4/8
These factors are not independent.
Differences in:
👥 populations
🧬 sequencing methods
💻 analytic pipelines
🌍 environments
all influence the observed microbiome and make comparisons across studies difficult.
🧵 3/8
Microbiome signals in TB are easily distorted.
⚕️ comorbidities
💊 antibiotics
🥗 nutrition
🌍 geography
🧪 sampling methods
Careful study design is essential to avoid misleading associations.
🧵 2/8
TB is not only a host–pathogen interaction.
It is a multi-layer ecological system involving:
🧬 host immunity
🫁 lung microbiome
🦠 gut microbiome
🌍 environmental exposures
These interactions may shape disease progression and recovery.
🧵 1/8 🧪
TB research has long focused on a single pathogen: Mycobacterium tuberculosis. 🦠
But TB unfolds within a complex microbial ecosystem. The human microbiome may influence susceptibility, inflammation, and treatment outcomes.
Our perspective ⬇️
🔗 t.ly/jMK3R
¡Gran iniciativa! Es clave que investigadores básicos y clínicos mantengamos el rigor y mensajes equilibrados.
El campo del microbioma es apasionante, pero sus aplicaciones clínicas siguen siendo muy limitadas.
Hoy, la utilidad de estas pruebas para decisiones clínicas es, como mucho, anecdótica.
Conexión MICROBIOMA presenta la infografía “Entender los test de microbioma: alcance y límites actuales”, un recurso divulgativo que explica qué analizan estas pruebas, cómo funcionan y sus limitaciones científicas y clínicas, recordando que no son diagnósticas y requieren asesoramiento profesional
💊 Las 3 veces que he comprado antibióticos en farmacias distintas me han ofrecido probióticos para “evitar complicaciones”.
📉 No hay evidencia sólida que respalde su uso sistemático en este contexto.
💰 Es un negocio lucrativo que no debería promoverse desde entornos sanitarios 🧪
10/10 🙏
Huge thanks to all participants, investigators, and INSTINCT/GESIDA10918 study sites.
Funded by Gilead/GESIDA (ISR-17-10294).
#HIV #HIVResearch #INSTINCT #ClinicalTrials #InfectiousDiseases
9/10 📚
Together with studies like SALSA, TANGO, iPrEx, and DISCOVER, INSTINCT reinforces that:
🔸 TDF has weight/lipid-suppressive effects
🔸 TAF shows no independent effects on weight
🔸 Modern regimens have comparable metabolic profiles
But results to date have not been uniform (PASODOBLE).
8/10 💭
As noted in the accompanying editorial by @JohnKoethe in the same CID issue: the discussion has evolved from "TAF promotes weight" → "TDF suppresses weight" → "TAF is neutral"
Our data support this latest conclusion.
doi.org/10.1093/cid/...
7/10 🔍
Why does this matter? For years, there was debate whether TAF had "obesogenic" properties when compared to TDF.
This study:
✅ Isolates TAF's effect (adding it to a 2-drug regimen) ✅ Eliminates confounders (no simultaneous changes in other ARVs)
6/10 🦠
Virologic efficacy: Maintained in >95% of participants in both groups. No differences in viral suppression or rebounds.
Safety: Well tolerated, mild and balanced adverse events.
5/10 💊
Metabolic profile: Minimal and similar changes in:
• Total cholesterol
• LDL/HDL
• Triglycerides
• Renal function (eGFR)
4/10 ⚖️
Weight: This is crucial. Annualized weight change:
• BIC/FTC/TAF: +0.3%
• DTG/3TC: +0.2%
No significant difference (p=0.895). Only 23% vs 17% gained ≥5% weight (p=NS).
3/10 📊
Inflammation 🔥: No significant differences in any inflammatory biomarker (sCD14, IL-6, D-dimer, sCD163, hsCRP, Kyn/Trp ratio) between groups over 96 weeks.
2/10 🎯
Design: 141 participants with virologic suppression on stable DTG/3TC were randomized 1:1 to:
• Continue DTG/3TC
• Switch to BIC/FTC/TAF
Follow-up: 96 weeks
Hypothesis: Could "intensification" to 3 drugs reduce residual inflammation and metabolic parameters?
1/10 🧵 Proud to share results from the INSTINCT trial, published in @cidjournal.bsky.social!
A randomized study addressing a key question: Does TAF have independent effects on weight and inflammation in people with HIV?
Spoiler: no
🧪
doi.org/10.1093/cid/...
Thanks to the organizers, assistants, international speakers and sponsors to keep alive this crucial event for the #HPV community in Spain 🤗
El @csic.es difunde la concesión de la ayuda de proyectos sinérgicos de la Comunidad de Madrid a nuestro compañero Dr. Bruno Sainz junto con el Dr. Sergio Serrano-Villar @serranovillar.bsky.social del #IRYCIS
Enhorabuena a los dos grupos de investigadores👏
@dicma-csic.bsky.social
“The Trump administration is, for the first time in history, substantially intervening inside NIH to bring it under political control,” according to a senior NIH official who spoke on condition of anonymity. My latest.
www.theguardian.com/us-news/2025...
🧠 Lithium and Alzheimer’s
A new study found that lithium protects the brain. In mice, early lithium loss triggered Alzheimer’s-like damage, but a special lithium salt reversed it.
🔗 www.nature.com/articles/s41...
#SciComm #Alzheimers 🧪
📣Bruno Sainz from #IIBM @csic.es receives substantial funding in the call for synergistic projects (CAM), together with @serranovillar.bsky.social -Ramón y Cajal Hospital/IRYCIS
➡️Reprogramming The Tumor Microenvironment Through Microbiome-Derived Immunomodulatory Molecules
Congratulations Bruno!!👏
🧬 Our new paper in TMAID: Chronic Chagas disease disrupts gut microbiome metabolism.
🔻 TCA, β-oxidation & haem pathways fall
🔺 Benznidazole partly restores microbial function
💡 Biomarkers & targets for microbiota therapies
📄 doi.org/10.1016/j.tm...
🙌@infecciosasryc.bsky.social #Chagas #Microbiome🧪
Beautiful research, thank you!🎉🎊
📣 HIV responses can’t hinge on political shifts.
✊🏾 We need stable, committed funding—not abandonment.🧪
#PEPFAR #HIV #FundingCrisis #GlobalHealth #IAS2025