pH-taxis drives aerobic bacteria in duodenum to migrate into the pancreas with tumors

Abstract

As oral or intestinal bacteria have been found in pancreatic cystic fluid and tumors, understanding bacterial migration from the duodenum into the pancreas via hepato-pancreatic duct is critical. Mathematical models of migration of aerobic bacteria from the duodenum to the pancreas with tumors were developed. Additionally, the bacterial distributions under the pH gradient and those under flow were measured in double-layer flow based microfluidic device and T-shaped cylinders. Migration of aerobic bacteria from the duodenum into pancreas is counteracted by bile and pancreatic juice flow but facilitated by pH-taxis from acidic duodenum fluid toward more favorable slightly alkaline pH in pancreatic juice. Additionally, the reduced flow velocity in cancer patients, due to compressed pancreatic duct by solid tumor, facilitates migration. Moreover, measured distribution of GFP E. coli under the pH gradient in a microfluidic device validated pH-tactic behaviors. Furthermore, Pseudomonas fluorescens in hydrochloride solution, but not in bicarbonate solution, migrated upstream against bicarbonate flow of > 20 μm/s, with an advancement at approximately 50 μm/s.

Intratumoral Microbiome: Foe or Friend in Reshaping Tumor Microenvironment Landscape?

“…In this vein, it was reported that intratumoral bacteria might migrate retrogradely from the duodenum to the pancreatic tissue through the pancreatic duct, in pancreatic ductal adenocarcinoma (PDAC) [61]. This migration is considered to be primarily reinforced by the pH gradient and to a lesser extent by the oxygen gradient between the two sites, conducting bacteria to the more neutral pH in the pancreatic tumor [62]. Another considerable source of intratumoral microbiome is the microbiome of the healthy tissue, adjacent to the tumor site, supported by the striking resemblance of their composition profile in many tumor types [17].…”

Three-dimensional microfluidic cell culture device that generates chemical and oxygen gradients

“…[5][6][7][8] On the other hand, microfluidic devices that generate chemical concentration gradients have also been proposed, in the hopes of mimicking cell chemotaxis, 9) which is the movement of cells following a specific chemical concentration gradient. [10][11][12] Devices that simultaneously form oxygen and chemical gradients have also been designed. 13) However, microfluidic devices that expose cells to gradients sufficient for visualizing microvascular networks or analyzing genes and proteins have not been developed.…”

Probiotic Spore-Based Oral Drug Delivery System for Enhancing Pancreatic Cancer Chemotherapy by Gut–Pancreas-Axis-Guided Delivery

“…The bacterial translocation in the pancreatic duct could be counteracted by the retrorse bile juice and pancreatic juice flows, which probably implies some impetus against obstructive bile and pancreatic juice for migration. Taking notice of the lower pH in duodenum fluid and slightly alkaline pH in pancreatic juice, we deduced that the pH gradient could support aerobes in targeting pancreatic tumors . Accordingly, the chemotaxis behaviors of mCherry-expressing E.…”

“…Taking notice of the lower pH in duodenum fluid and slightly alkaline pH in pancreatic juice, we deduced that the pH gradient could support aerobes in targeting pancreatic tumors. 35 Accordingly, the chemotaxis behaviors of mCherry-expressing E. coli (mCherry@EC) in four models with pH gradients were analyzed. 36 Through monitoring the red fluorescence protein mCherry, we observed that microbes spontaneously swam from bacterial solutions (low-pH side, pH = 5.5) into bacteria-free pipet tips (high-pH side, pH = 8.0) while they were unable to migrate from the high-pH side to the low-pH side (Figure 1f and Figure S8a).…”