Publications by authors named "Andrew Macpherson"

Background: The human microbiome is crucial in regulating intestinal and systemic functions. While its role in cardiovascular disease is better understood, the link between intestinal microbiota and valvular heart diseases (VHD) remains largely unexplored.

Methods: Peer-reviewed studies on human, animal or cell models analysing gut microbiota profiles published up to April 2024 were included.

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The small intestinal microbiota has a crucial role in gastrointestinal health, affecting digestion, immune function, bile acid homeostasis and nutrient metabolism. The challenges of accessibility at this site mean that our knowledge of the small intestinal microbiota is less developed than of the colonic or faecal microbiota. Here, we summarize the features and fluctuations of the microbiota along the small intestinal tract, focusing on humans, and discuss physicochemical factors and assessment methods, including the technical challenges of investigating the low microbial biomass of the proximal small bowel.

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After failed biliary cannulation standard endoscopic retrograde cholangiography approach, endoscopic-ultrasound-based rendezvous-endoscopic retrograde cholangiography (EUS-RV-ERC) is a valid alternative. One of the challenging factors in this setting is the management of the guidewire. Here, we propose a method, where a slim endoscope is used to stabilize the guidewire and optimize wire manipulation in a patient who underwent EUS-RV-ERC a transgastric approach.

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Background & Aims: Although chronic diarrhea and constipation are common, the treatment is symptomatic because their pathophysiology is poorly understood. Accumulating evidence suggests that the microbiota modulates gut function, but the underlying mechanisms are unknown. We therefore investigated the pathways by which microbiota modulates gastrointestinal motility in different sections of the alimentary tract.

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Article Synopsis
  • The study investigates the availability and accessibility of Automated External Defibrillators (AEDs) in four major regions of British Columbia (BC) to improve outcomes for out-of-hospital cardiac arrests (OHCA).
  • It analyzed data from 879 operational AEDs and 9333 EMS-treated OHCAs over five years, measuring factors like weekly accessible AED-hours per 100,000 population and the proximity of AEDs to OHCAs.
  • Results showed significant differences in AED access across regions, indicating a need for better strategic placement of AEDs to enhance community preparedness for cardiac emergencies.
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Background: Microbiota composition is fundamental to human health with the intestinal microbiota undergoing critical changes within the first two years of life. The developing intestinal microbiota is shaped by maternal seeding, breast milk and its complex constituents, other nutrients, and the environment. Understanding microbiota-dependent pathologies requires a profound understanding of the early development of the healthy infant microbiota.

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The enteric nervous system is largely autonomous, and the central nervous system is compartmentalized behind the blood-brain barrier. Yet the intestinal microbiota shapes gut function, local and systemic immune responses, and central nervous system functions including cognition and mood. In this review, we address how the gut microbiota can profoundly influence neural and immune networks.

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Macrophages are involved in immune defense, organogenesis and tissue homeostasis. Macrophages contribute to the different phases of mammary gland remodeling during development, pregnancy and involution postlactation. Less is known about the dynamics of mammary gland macrophages in the lactation stage.

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In early life, the intestinal mucosa and immune system undergo a critical developmental process to contain the expanding gut microbiome while promoting tolerance toward commensals, yet the influence of maternal diet and microbial composition on offspring immune maturation remains poorly understood. We colonized germ-free mice with a consortium of 14 strains, fed them a standard fiber-rich chow or a fiber-free diet, and then longitudinally assessed offspring development during the weaning period. Unlike pups born to dams fed the fiber-rich diet, pups of fiber-deprived dams demonstrated delayed colonization with Akkermansia muciniphila, a mucin-foraging bacterium that can also use milk oligosaccharides.

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Background & Aims: The progression of non-alcoholic steatohepatitis (NASH) to fibrosis and hepatocellular carcinoma (HCC) is aggravated by auto-aggressive T cells. The gut-liver axis contributes to NASH, but the mechanisms involved and the consequences for NASH-induced fibrosis and liver cancer remain unknown. We investigated the role of gastrointestinal B cells in the development of NASH, fibrosis and NASH-induced HCC.

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Distinct niches of the mammalian gut are populated by diverse microbiota, but the contribution of spatial variation to intestinal metabolism remains unclear. Here we present a map of the longitudinal metabolome along the gut of healthy colonized and germ-free male mice. With this map, we reveal a general shift from amino acids in the small intestine to organic acids, vitamins and nucleotides in the large intestine.

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Intestinal IL-17-producing T helper (Th17) cells are dependent on adherent microbes in the gut for their development. However, how microbial adherence to intestinal epithelial cells (IECs) promotes Th17 cell differentiation remains enigmatic. Here, we found that Th17 cell-inducing gut bacteria generated an unfolded protein response (UPR) in IECs.

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Article Synopsis
  • Maternal innate-like lymphocytes, particularly γδ T cells, play a crucial role in shaping the immune response of offspring during development, influencing inflammation and immune cell types.
  • Mice born to mothers lacking γδ T cells show heightened inflammation and a type 2 immune response, particularly after helminth infections, due to changes in their gut microbiota and levels of short-chain fatty acids (SCFAs).
  • Supplementing SCFAs can reduce inflammation and improve lung immunity in these offspring, highlighting the interplay between maternal immune cells, gut microbiota, and neonatal immune development.
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  • Scientists are debating whether a fetus and its surroundings are home to stable groups of tiny living things called microbes during a healthy pregnancy.
  • Recent studies suggest that when they find these microbes, it could be because of mistakes during the testing process, not that the fetus actually has them.
  • Understanding these findings is important for learning how our immune system develops and shows that studying tiny living things in places with very few of them can be really tricky, so we need to use different science methods to get it right.
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Given that available antidepressant pharmacotherapies are not optimally effective, there is a need for alternative treatment options that are rooted in a comprehensive understanding of the illness's pathophysiology. Major depressive disorder (MDD) has been historically attributed to monoamine, i.e.

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The human distal small intestine (ileum) has a distinct microbiota, but human studies investigating its composition and function have been limited by the inaccessibility of the ileum without purging and/or deep intubation. We investigated inherent instability, temporal dynamics, and the contribution of fed and fasted states using stoma samples from cured colorectal cancer patients as a non-invasive access route to the otherwise inaccessible small and large intestines. Sequential sampling of the ileum before and after stoma formation indicated that ileostoma microbiotas represented that of the intact small intestine.

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Immune cells generated in early life play pivotal roles for immune homeostasis in adulthood. Vergani et al. identify a population of early-life-origin IgA B cells that are maintained throughout life to achieve homeostasis in the adult gut.

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The capacity of the intestinal microbiota to degrade otherwise indigestible diet components is known to greatly improve the recovery of energy from food. This has led to the hypothesis that increased digestive efficiency may underlie the contribution of the microbiota to obesity. OligoMM12-colonized gnotobiotic mice have a consistently higher fat mass than germ-free (GF) or fully colonized counterparts.

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Secretory immunoglobulin A (SIgA) interaction with commensal bacteria conditions microbiota composition and function. However, mechanisms regulating reciprocal control of microbiota and SIgA are not defined. Bacteria-derived adenosine triphosphate (ATP) limits T follicular helper (Tfh) cells in the Peyer's patches (PPs) via P2X7 receptor (P2X7R) and thereby SIgA generation.

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Article Synopsis
  • Researchers used CRISPR technology to create engineered microbes that can store and record information from their environment, particularly gene expression changes.
  • These microbes can capture significant interactions between the host and its gut environment, including responses to dietary changes, inflammation, and the complexity of the gut microbiome.
  • The study employed Record-seq to track the transcriptional history of bacterial strains in the intestines, allowing for a deeper understanding of how genetic variations impact microbial adaptation without altering the host's physiology.
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  • Interactions between pathogens, host microbiota, and the immune system play critical roles in health and disease processes.
  • Widespread dermal vaccination with vaccinia virus (VACV) effectively eradicated smallpox, but its interaction with microbiota and effects on vaccination efficacy remain underexplored.
  • Vaccination with VACV leads to increased commensal bacteria at the infection site, which can cause more inflammation and tissue damage, yet genetic factors allow for protective immune responses similar across different microbiota states.
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Microglial function declines during aging. The interaction of microglia with the gut microbiota has been well characterized during development and adulthood but not in aging. Here, we compared microglial transcriptomes from young-adult and aged mice housed under germ-free and specific pathogen-free conditions and found that the microbiota influenced aging associated-changes in microglial gene expression.

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Innate lymphoid cells (ILCs) are important for tissue immune homeostasis, and are thoroughly characterized in mice and humans. Here, we have performed in-depth characterization of rat ILCs. Rat ILCs were identified based on differential expression of transcription factors and lack of lineage markers.

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