EP-4735647-A1 - BIOMARKER OF THE STATUS OF THE MICROBIOTA OF A FARM ANIMAL AND USES THEREOF

Abstract

The present invention relates to a use of one or more ratios of quantities of bacteria in the microbiota of a farm animal, said ratio(s) being selected from Firmicutes / Proteobacteria; Clostridium Clusters IV and XlVa / Enterobacteriaceae; Ruminococcaceae and Lachnospiraceae / Enterobacteriaceae ; butyrate-producing bacteria / Firmicutes ; aerobic bacteria / anaerobic bacteria, as as marker(s) to determine the status of the intestinal microbiota of a farm animal and whether it is satisfactory or unsatisfactory, or for selecting an extract of a satisfactory intestinal microbiota of a farm animal, intended to maintain or to improve the intestinal microbiota of a different farm animal in need thereof.

Inventors

• VIECO SAIZ, Nuria
• CONSUEGRA, Jessika

Assignees

• Adisseo France S.A.S.

Dates

Publication Date

20260506

Application Date

20240627

Claims (18)

1. 1. A use of one or more ratios of quantities of bacteria in the microbiota of a farm animal, to determine the status of the intestinal microbiota of a farm animal and whether it is satisfactory or unsatisfactory, said ratio(s) being selected from Firmicutes I Proteobacteria; Clostridium Clusters IV and XlVa / Enterobacteriaceae; Ruminococcaceae and Lachnospiraceae / Enterobacteriaceae; butyrate-producing bacteria / Firmicutes; aerobic bacteria / anaerobic bacteria,
2. 2. A use of one or more ratios of quantities of bacteria in the microbiota of a farm animal, for selecting an extract of a satisfactory intestinal microbiota of a farm animal, intended to maintain or to improve the intestinal microbiota of a different farm animal in need thereof.
3. 3. A use according to claim 1 or 2, of at least two, at least three, at least four, or all of said ratios.
4. 4. A method for determining in vitro or ex vivo a status of the intestinal microbiota of a farm animal, comprising at least the following steps: detecting and quantifying, in a biological sample of said farm animal, the bacteria selected from the Firmicutes, Proteobacteria, Clostridium Clusters IV and XlVa, Enterobacteria, Ruminococcaceae, Lachnospiraceae, butyrate-producing bacteria, aerobic bacteria and anaerobic bacteria; and calculating at least one ratio selected from Firmicutes / Proteobacteria, Clostridium Clusters IV and XlVa / Enterobacteriaceae, Ruminococcaceae and Lachnospiraceae / Enterobacteriaceae, butyrate producing bacteria / Firmicutes, and aerobic bacteria / anaerobic bacteria.
5. 5. Method according to claim 4, characterized in that it further comprises the following steps: comparing the or each of the ratios of said biological sample of said animal with a control value determined for each of said ratios, and determining the status of said microbiota from said comparison.
6. 6. Method according to claim 5, characterized in that it comprises calculating at least one ratio selected from Firmicutes / Proteobacteria, Clostridium Clusters IV and XlVa / Enterobacteriaceae, Ruminococcaceae and Lachnospiraceae / Enterobacteriaceae, butyrate-producing bacteria / Firmicutes, and if the ratio or each of the calculated ratios is greater than or equal to the control value determined for the corresponding ratio, then the status of the microbiota is qualified as satisfactory, and if the ratio or each of the ratios is lower than the control value, then the status of the microbiota is qualified as unsatisfactory.
7. 7. Method according to claim 5, characterized in that it comprises calculating at least the aerobic bacteria/anaerobic bacteria ratio, and if the ratio is less than or equal to the control value, then the status of the microbiota is qualified as satisfactory, and if the ratio is higher than the control value, then the status of the microbiota is qualified as unsatisfactory.
8. 8. Method according to any one of claims 4-7, characterized in that it comprises calculating and optionally comparing with a control value, at least two, at least three, or at least four of said ratios, or the five ratios.
9. 9. Method according to any one of claims 4 to 8, characterized in that the biological sample is selected from cecal content, ileal content and fecal content.
10. 10. Method according to any one of the claims 4-9, characterized in that the quantity of bacteria is measured by the relative abundances obtained from data resulting from the sequencing analysis by 16s rRNA sequencing.
11. 11 . Method according to any one of claims 4-10, characterized in that the farm animal is a chicken and that the control value of any of the following ratios Firmicutes I Proteobacteria; Clostridium Clusters IV and XlVa / Enterobacteriaceae; Ruminococcaceae and Lachnospiraceae / Enterobacteriaceae; butyrate-producing bacteria / Firmicutes; aerobic bacteria / anaerobic bacteria is determined for a same chicken which is not.
12. 12. Method according to any one of claims 4-11 , characterized in that the farm animal is a chicken and that the control value of the aerobic bacteria / anaerobic bacteria ratio is measured in a chicken under farm conditions that that is not or less challenged than the chicken which intestinal microbiota status is determined.
13. 13. Method for selecting an extract of a satisfactory intestinal microbiota of a farm animal, comprising the following steps: detecting and quantifying, in a biological sample of said farm animal, the quantity of each of the bacteria selected from Firmicutes, bacteria producing butyrate, aerobic bacteria and anaerobic bacteria and calculating at least one ratio selected from Butyrate-producing bacteria / Firmicutes (a1) and aerobic bacteria / anaerobic bacteria (a2); detecting and quantifying, in a biological sample of a different farm animal, the quantity of each of the bacteria selected from Firmicutes, bacteria producing butyrate, aerobic bacteria and anaerobic bacteria and calculating at least one ratio selected from butyrate-producing bacteria / Firmicutes (b1) and aerobic bacteria / anaerobic bacteria (b2); comparing the calculated ratios (a1) and (b1) and/or ratios (a2) and (b2); and selecting said satisfactory extract from said comparison.
14. 14. Method according to claim 13, characterized in that, if the butyrate-producing bacteria / Firmicutes ratio (a1) is greater than or equal to ratio (b1), and/or if the aerobic bacteria/anaerobic bacteria ratio (a2) is less than or equal to ratio (b2), said extract is selected.
15. 15. Non-therapeutic method for maintaining or improving the intestinal microbiota of a farm animal in need thereof, characterized in that it comprises the following steps: selecting a satisfactory microbiota extract according to the method of claim 13 or 14, and administrating to said farm animal, said satisfactory microbiota extract or a derivative thereof resulting from fermentation.
16. 16. Method according to claim 15, characterized in that the farm animal is young.
17. 17. Method according to claim 16, characterized in that the farm animal is a chick and it is administered an amount of 1-9.10 7 CFU of said extract.
18. 18. A biomarker of the status of the microbiota of a farm animal selected from the ratios of amounts of bacteria, Firmicutes / Proteobacteria; Clostridium Clusters IV and XlVa / Enterobacteriaceae; Ruminococcaceae and Lachnospiraceae / Enterobacteriaceae; butyrate-producing bacteria / Firmicutes; aerobic bacteria / anaerobic bacteria.

Description

BIOMARKER OF THE STATUS OF THE MICROBIOTA OF A FARM ANIMAL AND USES THEREOF The present invention relates to the field of livestock animals and more particularly pertains to an alternative way for improving their health. To mitigate the problems of health of farm animals is a major stake for any stockbreeder, in that it is definitively linked to high performance in terms of production and meat quality, and from an ethical point of view, to a better animal welfare. Animal’s growth performance is usually carried out by measuring zootechnical parameters such as body weight (BW), body weight gain (BWG), feed intake (Fl) and feed conversion ratio (FCR). Regarding the assessment of animal’s health, parameters are measured on the animals or their environment. Commonly used parameters are based on the detection of plasma proteins in the luminal fluid, of short chain fatty acids (SCFA) production in the gut microbiota, of lipopolysaccharides (LPS) in serum, of bacteria passing through the intestinal epithelium (bacterial translocation), etc. (Ducatelle, R.; Goossens, E.; De Meyer, F.; Eeckhaut, V.; Antonissen, G.; Haesebrouck, F.; van Immerseel, F. (2018) Biomarkers for monitoring intestinal health in poultry. Present status and future perspectives. In : Veterinary research, vol. 49, n° 1 , p. 43). Regarding external parameters it is usually measured by litter and pododermatitis scoring (Eichner, G.; Vieira, S. L.; Torres, C. A.; Coneglian, J.L.B.; Freitas, D. M.; Oyarzabal, O. A. (2007) Litter Moisture and Footpad Dermatitis as Affected by Diets Formulated on an All-Vegetable Basis or Having the Inclusion of Poultry By-Product. In : The Journal of Applied Poultry Research, vol. 16, n° 3, p. 344-350). Gastrointestinal tract (GIT) health and more specifically intestinal health is a key factor for general health and well-being of animals and consequently on production. In the context of livestock, animals face significant challenges, in particular due to the increase in farm size, ever faster growth, sensitive physiological stages, thus their performance can be significantly reduced. Resilience is the ability of animals to adapt in this challenging environment through greater resistance. More resilient animals will have more regular production and better welfare. MC Costa et al. Different antibiotic growth promoters (AGPs) induce specific changes in the cecal microbiota membership of broiler chicken, Pios One, vol. 12, no. 2 (2017) investigates the impact of five antibiotic growth promoters in broiler chicken. The evaluation was carried out in the cecal microbiota and it was observed changes in the specific bacterial members present in the cecum of the chickens. To this end, Firmicutes I Proteobacteria ratio was calculated and shows a lower value in the treated group compared to the control group. However, these results evidence that these AGPs have a strong influence on the rare species of bacteria present in cecal microbiota, but no influence on commensal bacteria and in particular on Firmicutes such Clostridium, Lactobacillus and Ruminococcus spp. In accordance with the present invention, it was discovered that determined microbial ratios of intestinal microbiota can be used, on the one hand, as a biomarker of the status of this microbiota and, on the other hand, for selecting microbial inocula having applications such as for maintaining or improving the GIT health of farm animals or for developing resilience of young animals that will grow under farming conditions. Thereby, the invention lies about the use of one or more ratios of quantities of bacteria in the microbiota of a farm animal, said ratio(s) being selected from Firmicutes / Proteobacteria; Clostridium Clusters IV and XlVa / Enterobacteriaceae; Ruminococcaceae and Lachnospiraceae / Enterobacteriaceae; butyrate-producing bacteria / Firmicutes; aerobic bacteria / anaerobic bacteria, In an aspect, the invention relates to the use of said ratio(s) as marker(s) to determine the status of the intestinal microbiota of a farm animal and whether it is satisfactory or unsatisfactory. In an embodiment, the invention relates to the use of at least two, at least three, at least four, or all of said ratios. In a further aspect, the invention pertains to the use of said ratio(s) for selecting an extract of a satisfactory intestinal microbiota of a farm animal, said extract being intended to maintain or to improve the intestinal microbiota of a farm animal in need thereof, the latter being different from the farm animal from which said extract comes from. In an embodiment, the invention aims at a biomarker of the status of the microbiota of a farm animal, said biomarker being selected from the following ratios of amounts of bacteria, Firmicutes / Proteobacteria, Clostridium Clusters IV and XlVa / Enterobacteriaceae, Ruminococcaceae and Lachnospiraceae / Enterobacteriaceae, butyrate producing bacteria / Firmicutes, and aerobic bacteria / anaerobic bacteria. The calcula