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Method and kit for the non-invasive evaluation of the
physiological state of the gastric mucosa
Background
Gastric mucosa, the mucous layer of the stomach, is a complex tissue playing a crucial role in the
digestion process and in the correct nutrition of the individual. It constitutes the first barrier of the
gastrointestinal track. But it is a fragile structure that can be subjected to pathologies (e.g. gastritis)
and lesions (e.g. ulcers).
Cellular exfoliation of the epithelium facing the lumina is essential for the stomach mucosa renewal
process. Exfoliation is crucial to maintain the architecture of the tissue and is an active biochemical
process related to the epithelium homeostasis. Like many other human biological functions
(digestive, metabolic, renal or respiratory), gastric exfoliation is modulated during the day: it is
regulated by the circadian rhythm but also synchronized by mealtimes, alternation of day and night,
or rhythms of monitoring and health care. Exfoliation rates are also sensitive to stresses, food intake
quality and medication: deregulation of exfoliation rhythm and rate is reported as a side effect of
some medical treatments (e.g. repeated aspirin or ibuprofen administration, chemotherapy).
Therefore, gastric exfoliation monitoring would represent a direct way to appreciate the
nutritional or pharmacological stress induced by a substance on the epithelium’s
homeostasis.
Assessing the physiological status of the gastric mucosa would also be very helpful to adapt
the feeding procedures currently used for premature infants: indeed, as the gastrointestinal
track of the preterm child is not ready for oral nutrition, the new born is usually fed with a naso-gastric
probe to ensure the transition from enteral nutrition to oral feeding. Furthermore, as the baby cannot
tolerate undigested milk, the stomach contents are emptied every three hours. These fluids contain
exfoliated cells which analysis would help to determine the degree of maturity of the stomach, and to
define the time at which the baby can be orally fed. However, such method is still cruelly missing.
Description of the innovation & industrial applications
The invention deals with a non-invasive method to follow the physiological status of the gastric
mucosa by studying the exfoliated cells recovered from patient’s gastric fluid. Gastric fluid is already
frequently collected in numerous clinical situations (aspirates of gastric fluids via a nasogastric tube,
or follow up of adult patients recovering from ulcers), especially during the above mentioned cares
provided to the preterm child.
INRA’s researchers and clinicians from the Mother and Child university hospital center (University of
Nantes, France) have reported a method to characterize exfoliated cells contained in a gastric fluid
using a set of specific biomarkers:
 Marker of gastric cell identity: gastric cells are discriminated among others cells contained in the recovered fluid for their expression of the gastric pump H+/K+-ATPase at their surface;
 Physiological state markers of exfoliated cells: o the SURVIVIN and LC3 proteins are two reliable markers of autophagy, a recycling
process of cells’ own cytoplasmic components induced when the cell has lost contact with the tissue architecture; o the biological clock markers PERIOD1 and CLOCK proteins can be used to
characterize exfoliation cycles and assess the rate of exfoliation over a period of several days. Indeed, the genes encoding these proteins are known to be involved in the regulation of the cell circadian rhythm. Siège social : 28, rue du Dr. Finlay - 75015 Paris - Tél. : 01 42 75 95 00 - Télécopie : 01 45 77 63 90 - Société Anonyme au capital de 1 829 388 € - RCS PARIS B 433 960 762 - SIRET : 433 960 762 00030 - APE 6630Z - TVA FR 96 433 960 762 Portefeuille d’offres de technologie d’INRA Transfert: http://www.inra-transfert.fr/ The invention provides a method to follow up gastric mucosa state evolution by using a
combination of antibodies specific to these markers to trace the gastric epithelial cells. The
analysis is a simple antigen-antibody reaction that can be performed using microscopy imaging,
cytometry, ELISA test or a protein chip.
The invention also discloses a method to isolate cells from gastric fluid extracts to be used to
assess the gastric mucosa physiological state; the method was assessed on the gastric contents of
rat pups and preterm children.
The present invention finds applications in clinical medicine, and more precisely in the domains of
pediatrics, nutrition, and personalized medication:
 Monitoring the maturation state of the gastric mucosa of the preterm child in order to adapt the medical feeding procedures to the child condition by: o Exploring the time course of exfoliation from birth to evaluate if the child is ready to be orally fed (i.e. assessing the best moment for naso-gastric tube removal); o Assess food intake (frequency, milk formula) effect on gastric epithelium’s exfoliation o Evaluate the parietal cell mass which is related to ulceration and increased acid secretion; specifically to preterm babies, parietal cell exfoliation may allow to follow sex related stomach maturation; o Following up the set up of the circadian rhythm in the gastric mucosa cell renewal  Monitoring the response of the gastric epithelium to food intake or pharmacological agents (e.g. follow up of nutrient cycle induced exfoliation, cancer patient nutritional management).
Intellectual property & Business proposal
Results and applications are patent pending (FR 1054245; priority date: 06/01/2010; extended
internationally through PCT WO2011/151344 A1 ; patents filled by INRA, the CHU of Nantes and the
University of Nantes, France).
INRA is interested in a partnership with companies in the field of clinical diagnosis. Any request
should be addressed to INRA Transfert which is in charge with the transfer of this technology
(license; license option with collaborative research programme).
Reference
 Kaeffer B, Legrand A, Moyon T, Frondas-Chauty A, Billard H, Guzman-Quevedo O, Darmaun, Rozé JC. (2011) Non invasive exploration of neonatal gastric epithelium by using exfoliated epithelial cells PLoS ONE 6(10) www.plosone.org e25562
Principal Investigator
Licensing Officer
Laboratory
UMR-1280, Physiologie des adaptations Fax: +33 (0)1 45 77 63 90 Email: alice.agasse@paris.inra.fr Siège social : 28, rue du Dr. Finlay - 75015 Paris - Tél. : 01 42 75 95 00 - Télécopie : 01 45 77 63 90 - Société Anonyme au capital de 1 829 388 € - RCS PARIS B 433 960 762 - SIRET : 433 960 762 00030 - APE 6630Z - TVA FR 96 433 960 762 Portefeuille d’offres de technologie d’INRA Transfert: http://www.inra-transfert.fr/

Source: http://www.inra-transfert.fr/en/pdf/INRA_Transfert_s_technology_offer_Kit_for_the_non_invasive_evaluation_of_the_physiological_state_of_the_gastric_mucosa_vFLG280912.pdf