Enhancement of Microbiota in Healthy Macaques Results in Beneficial Modulation of Mucosal and Systemic Immune

Jennifer A Manuzak1, Tiffany Hensley-McBain1, Alexander S Zevin1

  • 1Department of Pharmaceutics, University of Washington, Seattle, WA 98121; Washington National Primate Research Center, Seattle, WA 98121;

Insights

Probiotic VSL#3 enhances mucosal immunity by increasing IgA-producing B cells and T follicular helper cells in macaques. This probiotic therapy may improve vaccine efficacy and mucosal protection against infection.

Area of Science:

  • Immunology
  • Microbiology
  • Gastroenterology

Background:

  • Mucosal surfaces are key sites for infection susceptibility.
  • Probiotics (PBio) modulate gut microbiota to improve health.
  • Understanding probiotic effects on mucosal immunity is crucial for vaccine development.

Purpose of the Study:

  • To assess the longitudinal impact of daily VSL#3 probiotic treatment on cellular and humoral immunity and inflammation in healthy macaques.
  • To elucidate the mechanisms by which probiotics enhance mucosal immune defenses.

Main Methods:

  • Daily VSL#3 probiotic administration to healthy macaques.
  • Analysis of immune cell populations (B cells, T follicular helper cells, APCs) in the colon and lymph nodes.
  • Measurement of IgA expression and inflammatory markers.
  • Assessment of HEK293 cell responses to Toll-like receptor (TLR) agonists.

Main Results:

  • VSL#3 significantly increased IgA-expressing B cells in the colon and lymph nodes.
  • Elevated T follicular helper cell frequencies and lymph node follicles were observed.
  • Increased frequencies of IL-23(+) antigen-presenting cells (APCs) in the colon correlated with T follicular helper cells.
  • VSL#3 downmodulated responses of TLR2, TLR3, TLR4, and TLR9-expressing cells to specific stimuli.

Conclusions:

  • Probiotic VSL#3 enhances mucosal immune responses, including IgA production and T follicular helper cell activity.
  • These findings suggest a mechanism for probiotic benefits on mucosal health.
  • Probiotic therapy may be a valuable strategy to augment vaccine efficacy and enhance protection against mucosal infections.

Related Concept Videos

Development of Human Microbiota01:30

Development of Human Microbiota

The human microbiota begins developing at birth and undergoes continual change as we age. Infancy marks a critical period of microbial sensitivity, offering a “window of opportunity” during which beneficial microbes help mature the immune system. By age three, children typically develop a more stable and diverse microbial community. Newborns acquire microbes from their immediate environment; vaginal delivery favors maternal vaginal microbes, while cesarean births favor microbes from...
17
The Oral Microbiota01:27

The Oral Microbiota

The oral microbiome includes a complex ecosystem comprising over 700 microbial species, identified through genomic sequencing and culture-based analyses to date. This community includes a core microbiome, found universally among individuals, and a variable component influenced by environmental factors such as diet, lifestyle, and host genetics. Site-specific conditions, including oxygen gradients, pH levels, and nutrient availability, determine the spatial distribution of these microorganisms...
14
Functions of the Gut Microbiota01:18

Functions of the Gut Microbiota

The gut microbiota includes trillions of microorganisms that colonize the human gastrointestinal tract, including bacteria, archaea, viruses, and fungi. This complex ecosystem plays a critical role in maintaining intestinal and systemic health. Most of these microbes inhabit the large intestine, establishing a relatively stable and diverse community that contributes to gut homeostasis through various metabolic, immunological, and protective mechanisms.Dominant bacterial phyla, such as...
24
Introduction to the Human Microbiota01:22

Introduction to the Human Microbiota

Microorganisms colonize various regions of the human body, including the mouth, nasal passages, throat, stomach, intestines, urogenital tract, and skin. The total number of microbial cells is estimated to range from 10¹³ to 10¹⁴—comparable to, or exceeding, the number of human somatic cells. This host–microbiome relationship has led to the conceptualization of humans as supraorganisms, wherein microbial communities perform vital roles in development, immunity,...
44
Probiotics01:22

Probiotics

Probiotics are live, non-pathogenic microorganisms that confer health benefits by modulating the gut microbiota. The human gastrointestinal tract harbors a complex microbial ecosystem, and the balance of this microbiota is crucial for digestive and systemic health. Among the most extensively studied and utilized probiotics are species formerly classified within the genera Lactobacillus and Bifidobacterium. These organisms not only naturally colonize the human gut but are also consumed through...
68
Gut-Brain Axis01:22

Gut-Brain Axis

The gut–brain axis is a bidirectional communication system that connects the gastrointestinal tract and the brain. This interaction is mediated through multiple pathways, including the vagus nerve, hormonal signals, immune responses, and chemical messengers produced by gut microbes.Microbial Contributions to Brain FunctionGut microbiota contributes significantly to brain function by producing neuroactive compounds. These include neuroactive compounds that influence neurotransmitters such...
39