GB2318978A

GB2318978A - Recolonisation of intestinal tract with microflora

Info

Publication number: GB2318978A
Application number: GB9723384A
Authority: GB
Inventors: Nigel T Plummer
Original assignee: CULTECH Ltd
Current assignee: CULTECH Ltd
Priority date: 1996-11-06
Filing date: 1997-11-06
Publication date: 1998-05-13
Also published as: GB9623068D0; GB9723384D0; CA2220659A1

Abstract

A method of restoring microflora to the intestinal tract following antibiotic therapy uses beneficial microbes which are administered in a treatment delivery medium to produce a beneficial microflora growth rate in excess of the natural growth rate. Therefore the intestinal tract is recolonised by beneficial microbes before other less desirable microbes are able to do so.

Description

Microflora The present invention relates to the management of beneficial microflora in the intestinal tract, particularly, but not exclusively, the human intestinal tract.

Antibiotics are commonly used for killing the disease-causing organisms at which they are targeted, but are scientifically proven to have a major deleterious effect on both the types and numbers of beneficial bacteria (the normal "microflora"). These beneficial bacteria such as Lactobacillus acidophilus and Bifidobacterium bifidum, are a very normal component of the intestinal tract and are established very soon after birth. They are generally a stable population and whilst they may impart several benefits to human health, it is generally considered that their major function is to help protect the body against invasion by harmful microorganisms. They do this primarily by covering the entire surface of the intestinal lining (almost like a carpet) either by direct attachment, or by populating the mucous layer which constantly flows over the surface of the lining. In either case they form a physical barrier to infection. During a course of antibiotics this "carpet" of beneficial bacteria can be virtually wiped out, leaving the intestinal lining unprotected.

Following completion of the course of antibiotics, the exposed gut lining is quickly re-colonised (this takes about two weeks). In many cases, this growback is accomplished by the beneficial flora, but very frequently this re-growth can include two very undesirable elements, namely opportunistic pathogens and antibiotic resistant bacteria.

Pathogens can often outgrow the normal flora with the result that diarrhoea (amongst other ailments) can occur. This can sometimes be persistent, becoming a chronic problem in some individuals. Overgrowth of the yeast organism which causes "thrush" is another common side effect of antibiotic therapy. This occurs in the intestinal tract just as commonly as in the genito-urinary tract.

Another problem, and one of the most major problems currently facing global human healthcare, is the increase in the number of harmful types of bacteria which are resistant to antibiotics. This problem has now reached the point where some very dangerous microbes e.g. multiple resistant Staph. aureus and multiple resistant Mycobacterium tuberculosis are either unaffected or resistant to virtually all known antibiotics. In the next ten years, there will be several well known and very harmful disease causing bacteria which will be resistant to all known antibiotics - these organisms will then be able to cause disease with no easy remedy available.

It is now established that many of these pathogens can acquire resistance to antibiotics by transfer of the relevant genetic material from the normal bacteria in the gut (which are themselves harmless) who have themselves acquired it from exposure to the original antibiotic therapy. It is therefore very desirable to minimise the numbers of bacteria in the gut which carry this resistance.

The present invention seeks to address these problems associated with antibiotic treatment.

According to a first aspect of the invention, there is provided a method of restoring microflora to the intestinal tract following antibiotic therapy, in which sufficient beneficial microbes are administered to produce beneficial microflora growth at a rate in excess of the natural growth rate, the beneficial microbes being repeatedly administered over a first predetermined period.

The first period is preferably at least one week. Administration preferably begins no more than a second predetermined period after the cessation of antibiotic therapy. The second period is preferably two weeks.

Beneficial microbes are preferably administered at a rate of at least 10 billion, preferably at least 25 billion, viable microbes per day. (In this specification, the term "billion" is used to mean 109 in line with common practice in this field, as will be appreciated by the appropriately skilled person).

The beneficial microbes are preferably naturally occurring in the human gut and may comprise members of the genera Lactobacillus and/or Bifidobacteria.

Preferably the microbes are beneficial to the human intestinal tract and are preferably prepared by isolation from a human subject or subjects.

The microbes may be presented in capsule or powder form.

In a second aspect, the invention provides the use of beneficial microbes for restoring microflora to the intestinal tract following antibiotic therapy, in which sufficient beneficial microbes are administered to produce beneficial microflora growth at a rate in excess of the natural growth rate, the beneficial microbes being repeatedly administered over a first predetermined period. The use may have any of the preferred features set out above in relation to the first statement of invention.

In a third aspect, the invention provides a treatment delivery medium for use in restoring microflora to the intestinal tract following antibiotic therapy, the medium comprising sufficient beneficial microbes for administration to produce beneficial microflora growth at a rate in excess of the natural growth rate, by repeated administration over a first predetermined period. The first period may be at least one week and preferably begins no more than a second predetermined period, preferably two weeks, after the cessation of antibiotic therapy. Preferably the beneficial microbes are sufficiently concentrated to allow administration at the rate of at least 10 billion, preferably at least 25 billion, viable microbes per day. The microbes are preferably naturally occurring in the human gut and may comprise members of the genera Lactobacillus and/or Bifidobacteria. Preferably the administered microbes are prepared by isolation from a human subject or subjects and are preferably beneficial to the human intestinal tract.

In a fourth aspect, the invention provides the use of beneficial microbes for manufacture of a medium for restoring microflora to the intestinal tract following antibiotic therapy, in which beneficial microbes are incorporated into a medium for administration at a rate which produces beneficial microflora growth at a rate in excess of the natural growth rate by repeated administration over a first predetermined period. The medium may have any of the preferred features set out above in relation to the third aspect of the invention.

Examples of implementation of the invention will now be described in more detail, by way of example only, and with reference to the accompanying drawing which is a highly schematic diagram illustrating the techniques to which this invention relates.

As has been noted above, there is a critical period of approximately two weeks following completion of antibiotic therapy, when the community of microorganisms grows back to the type of numbers which are considered normal. This growth is largely unstructured and can result in significantly higher numbers of potentially harmful bacteria in the population and also significantly higher numbers of antibiotic resistant bacteria. The invention addresses this by seeking to manage the re-growth of the normal flora.

The drawing illustrates how the invention envisages this being achieved.

Beneficial bacteria such as Lactobacillus acidophilus and Bifidobacterium bifidum are cultured at 10, preferably having been collected from a human subject 12. The culture is then incorporated into a delivery medium 14a,14b before administration to a human subject 16. The medium 14a is illustrated as a capsule into which live beneficial bacteria are incorporated and which can then be swallowed by the subject 16. The medium 14b is illustrated as a yoghurt or other dairy product into which the beneficial bacterial are incorporated and which can then be ingested by the subject 16 in the normal way. Another type of medium 14 could be a powder, which could be taken by sprinkling onto a foodstuff or into a drink.

It is important that the subject 16 begins taking the medium 14 within a first predetermined period following antibiotic therapy, preferably within two weeks. The concentration of beneficial microbes in the medium 14 should be sufficiently high to allow the subject 16 to receive these at the rate of at least 10 billion viable microbes per day. That is, a convenient number of capsules 14a (one or a few), or a convenient portion size of product 14b should deliver this number of microbes. Although the precise number of microbes may be varied, it is expected that at least 10 billion microbes per day would be required, but that preferably at least 25 billion microbes per day would be administered. This should be by at least one dose per day.

Administering at this rate encourages the re-growth of beneficial microbes at a significantly greater rate than would occur naturally (unaided), and allows the beneficial microbes to re-colonise the intestinal tract before other microbes are able to do so, thereby blocking those others from doing so.

The beneficial microbes used are preferably those naturally occurring in the human gut, preferably including members of the genera Lactobacillus and/or Bifidobacteria.

While it has been suggested above that the start of administration of beneficial microbes can be delayed until two weeks after the cessation of antibiotic therapy, an earlier start to the administration could be beneficial and indeed, administration could begin during the antibiotic therapy. In either case, the administration of microbes should continue for at least one week after the cessation of the antibiotic course and should not begin more than two weeks after the end of the antibiotic course.

Many variations and modifications to what has been described can be achieved without departing from the scope of the present invention. In particular, many other delivery media could be envisaged and could administer various beneficial bacteria or combinations thereof.

Whilst endeavouring in the foregoing specification to draw attention to those features of the invention believed to be of particular importance it should be understood that the Applicant claims protection in respect of any patentable feature or combination of features hereinbefore referred to and/or shown in the drawings whether or not particular emphasis has been placed thereon.

Claims

Claims:

1. A method of restoring microflora to the intestinal tract following antibiotic therapy, in which sufficient beneficial microbes are administered to produce beneficial microflora growth at a rate in excess of natural growth rate, the beneficial microbes being repeatedly administered over a first predetermined period.

2. A method according to claim 1, wherein the first period is at least one week.

3. A method according to claims 1 or 2, wherein administration begins no more than a second predetermined period after the cessation of antibiotic therapy.

4. A method according to claim 3, wherein the second period is two weeks.

5. A method according to any of claims 1 to 4, wherein beneficial microbes are administered at a rate of at least 10 billion viable microbes per day.

6. A method according to any of claims 1 to 4, wherein beneficial microbes are administered at a rate of at least 25 billion viable microbes per day.

7. A method according to any preceding claim, wherein the beneficial microbes are naturally occurring in the human gut.

8. A method according to any preceding claim, wherein the beneficial microbes comprise members of the genera Lactobacillus and/or Bifidobacteria.

9. A method according to any preceding claim, wherein the microbes are beneficial to the human intestinal tract.

10. A method according to any preceding claim, wherein the microbes are prepared by isolation from a human subject or subjects.

11. A method according to any preceding claim, wherein the microbes are presented in capsule or powder fonn.

12. The use of beneficial microbes for restoring microflora to the intestinal tract following antibiotic therapy, in which sufficient beneficial microbes are administered to produce beneficial microflora growth at a rate in excess of the natural growth rate, the beneficial microbes being repeatedly administered over a first predetermined period.

13. A use according to claim 12, wherein the first period is at least one week.

14. A use according to claim 12 or 13, wherein administration begins no more than a second predetermined period after the cessation of antibiotic therapy.

15. A use according to claim 14, wherein the second period is two weeks.

16. A use according to any of claims 12 to 15, wherein beneficial microbes are administered at a rate of at least 10 billion viable microbes per day.

17. A use according to any of claims 12 to 15, wherein beneficial microbes are administered at a rate of at least 25 billion viable microbes per day.

18. A use according to any of claims 12 to 17, wherein the beneficial microbes are naturally occurring in the human gut.

19. A use according to any of claims 12 to 18, wherein the beneficial microbes comprise members of the genera Lactobacillus and/or Bifidobacteria.

20. A use according to any of claims 12 to 19, wherein the microbes are beneficial to the human intestinal tract.

21. A use according to any of claims 12 to 20, wherein the microbes are prepared by isolation from a human subject or subjects.

22. A use according to any of claims 12 to 21, wherein the microbes are presented in capsule or powder form.

23. A treatment delivery medium for use in restoring microflora to the intestinal tract following antibiotic therapy, the medium comprising sufficient beneficial microbes for administration to produce beneficial microflora growth at a rate in excess of the natural growth rate, by repeated administration over a first predetermined period.

24. A treatment delivery system according to claim 23, wherein the first period is at least one week.

25. A treatment delivery system according to claim 23 or 24, wherein the first period begins no more than a second predetermined period after the cessation of antibiotic therapy.

26. A treatment delivery system according to claim 25, wherein the second predetermined period is two weeks.

27. A treatment delivery system according to any of claims 23 to 26, wherein the beneficial microbes are sufficiently concentrated to allow administration at the rate of at least 10 billion viable microbes per day.

28. A treatment delivery system according to any of claims 23 to 26, wherein the beneficial microbes are sufficiently concentrated to allow administration at the rate of at least 25 billion viable microbes per day.

29. A treatment delivery system according to any of claims 23 to 28, wherein the microbes are naturally occurring in the human gut.

30. A treatment delivery system according to any of claims 23 to 29, wherein the microbes comprise members of the genera Lactobacillus and/or Bifidobacteria.

31. A treatment delivery system according to any of claims 23 to 30, wherein the administered microbes are beneficial to the human intestinal tract.

32. A treatment delivery system according to any of claims 23 and 31, wherein the administered microbes are prepared by isolation from a human subject or subjects.

33. A treatment delivery system according to any of claims 23 to 32, wherein the microbes are presented in capsule or powder form.

34. The use of beneficial microbes for manufacture of a medium for restoring microflora to the intestinal tract following antibiotic therapy, in which beneficial microbes are incorporated into a medium for administration at a rate which produces beneficial microflora growth at a rate in excess of the natural growth rate by repeated administration over a first predetermined period.

35. A use according to claim 34, wherein the first period is at least one week.

36. A use according to claim 34 or 35, wherein the first period begins no more than a second predetermined period after the cessation of antibiotic therapy.

37. A use according to claim 36, wherein the second predetermined period is two weeks.

38. A use according to any of claims 34 to 37, wherein the beneficial microbes are sufficiently concentrated to allow administration at the rate of at least 10 billion viable microbes per day.

39. A use according to any of claims 34 to 38, wherein the beneficial microbes are sufficiently concentrated to allow administration at the rate of at least 25 billion viable microbes per day.

40. A use according to any of claims 34 to 39, wherein the microbes are naturally occurring in the human gut.

41. Use according to any of claims 34 to 40, wherein the microbes comprise members of the genera Lactobacillus and/or Bifidobacteria.

42. Use according to any of claims 34 to 41, wherein the administered microbes are beneficial to the human intestinal tract.

43. Use according to claims 34 and 42, wherein the administered microbes are prepared by isolation from a human subject or subjects.

44. A use according to any of claims 34 to 43, wherein the microbes are presented in capsule or powder form.

45. A method of restoring microflora substantially as described above, with reference to the accompanying drawings.

46. Any novel subject matter or combination including novel subject matter disclosed, whether or not within the scope of or relating to the same invention as any of the preceding claims.