Altered Duodenal Mucosa-Associated Microbiota and Immune Profiles in Functional Dyspepsia: A Study of Host-Microbiome Homeostasis.

Functional dyspepsia patients had decreased villi goblet cells compared to controls.

• Upper gastrointestinal biopsies were collected from 11 outpatient controls and 17 FD patients.
• Histological analysis of duodenal biopsies revealed significantly decreased villi goblet cells in FD patients.
• Biopsies were collected for 16S rRNA sequencing, histology, and mucosal lamina propria mononuclear cell (LPMC) isolation.

FD patients showed increased LPMC CD4 Central Memory T-cell populations compared to controls.

• PBMC and LPMC populations were analyzed for T-cell populations by flow cytometry.
• Increased LPMC CD4 Central Memory was identified as a significant difference between FD patients and controls.
• The study compared immune measures between 17 FD patients and 11 controls.

FD patients showed increased LPMC CD8 T-cell populations compared to controls.

• Increased LPMC CD8 was identified as a significant difference in FD patients compared to controls.
• Flow cytometry was used to analyze LPMC populations.
• In FD patients, LPMC CD8 demonstrated a significant negative correlation with Sulfophobococcus.

FD patients showed increased PBMC CD4+ Central Memory Th17 cells compared to controls.

• Increased PBMC CD4+ Central Memory Th17 was identified as a significant difference in FD patients.
• Where available, peripheral blood mononuclear cells (PBMC) were isolated and analyzed by flow cytometry.
• In FD patients, PBMC CD4+ Central Memory Th17 positively correlated with both Gemella and Fusobacterium.

In control subjects, villi goblet cells positively correlated with Massilia and negatively correlated with Exiguobacterium in the duodenal mucosa-associated microbiota.

• 16S rRNA sequencing was used to profile the duodenal mucosa-associated microbiota (d-MAM).
• These correlations between goblet cells and specific microbiota were present in controls but were not reported to be present in FD patients.
• The cohort included 11 outpatient controls.

In control subjects, LPMC CD4 Central Memory T-cells negatively correlated with Veillonella, an association absent in FD patients.

• The negative correlation between LPMC CD4 Central Memory and Veillonella was specific to the control population.
• The absence of this association in FD patients was interpreted as suggesting a loss of host-microbiome homeostasis.
• This finding was identified through microbiome-immune correlation analyses using 16S rRNA sequencing and flow cytometry data.

Immune-microbiome associations present in control populations were absent in FD patients, suggesting a loss of host-microbiome homeostasis.

• Controls demonstrated specific correlations between microbial taxa and immune/histological measures (Massilia, Exiguobacterium with goblet cells; Veillonella with LPMC CD4 Central Memory) that were not observed in FD patients.
• FD patients instead showed distinct correlations including LPMC CD8 with Sulfophobococcus, and PBMC CD4+ Central Memory Th17 with Gemella and Fusobacterium.
• The authors conclude these findings indicate 'a loss of host-microbiome homeostasis that may contribute to FD pathophysiology.'