Therapeutic compositions and methods

Abstract

The present invention relates to reducing methane production in humans, in particular humans suffering from irritable bowel syndrome. In particular, the present invention relates to a virus capable of inhibiting in vivo methane formation in the gastrointestinal tract of a human for use in a method of reducing methane production in a human subject. The present invention also relates to a pharmaceutical composition comprising a virus capable of reducing in vivo methane formation in the gastrointestinal tract of a human, and the use of these pharmaceutical compositions in a method of reducing methane production in a human. The present invention also relates to a method of reducing methane production in a human, the method comprising administering to the human a virus capable of inhibiting in vivo methane production in the gastrointestinal tract.

Description

Technical Field

[0001] This invention relates to reducing methane production in humans, particularly those suffering from irritable bowel syndrome (IBS). Specifically, this invention relates to viruses capable of inhibiting methane formation in the human gastrointestinal tract, used in methods for reducing methane production in human subjects. The invention also relates to pharmaceutical compositions comprising viruses capable of reducing methane formation in the human gastrointestinal tract, and the use of these pharmaceutical compositions in methods for reducing methane production in humans. Furthermore, the invention relates to a method for reducing methane production in humans, the method comprising administering to a human a virus capable of inhibiting methane production in the gastrointestinal tract. Background Technology

[0002] Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder that affects the digestive tract, with an estimated global prevalence of 12%. The disease affects women approximately twice as often as men and is most common in people under the age of 45.

[0003] IBS patients exhibit significant variations in stool characteristics, leading to three main subtypes: diarrheal IBS (D-IBS), constipation-related IBS (C-IBS), and mixed IBS (M-IBS). The fecal microbial composition of IBS patients varies depending on stool quality and IBS classification. Stool consistency is closely related to fecal microbial community diversity; individuals with firmer stools exhibit higher species richness, which gradually decreases within the range of stool characteristics, reaching its lowest point in individuals with diarrhea.

[0004] Methanogenic archaea (commonly known as methanogens) are the main biological source of methane in nature, and *Methanobacterium spp.* (also known as *Methanogens spp.*) Methanobrevibacter smithii Methanogens are the main methanogens in the human gut. These methanogens can comprise up to 10% of the gut microbiome and are present in the colon, but they can also be shown to colonize the small intestine, particularly when small intestinal bacteria overgrowth. Increased abundance of these methanogens has been found in the harder stools of patients with chronic IBS compared to those with diarrhea in patients with D-IBS, and elevated methane production is associated with constipation. In fact, methane is a putative neurotransmitter that acts on the cholinergic pathway of the enteric nervous system, thereby delaying the intestinal transit time of ingested food and promoting segmental (non-diffuse) peristaltic contractions.

[0005] IBS is a significant nursing concern because it greatly impacts patients' quality of life. Specifically, C-IBS can negatively affect overall well-being through abdominal pain, bloating, and changes in bowel habits. Given that C-IBS patients experience increased methane production due to an increased abundance of methanogens, reducing methane production in these patients is a treatment strategy for symptom relief. Previously, this was done using medications (such as the prodrug lactone form of lovastatin) or antibiotics (such as rifaximin and neomycin). However, these medications have drawbacks because they disrupt the gut microbiome through indiscriminate action. Therefore, a more targeted strategy is needed to reduce methane production in patients with IBS, particularly those with C-IBS, as elevated methane production is associated with adverse symptoms including discomfort from bloating and constipation, and reducing methane production in these patients would improve their quality of life. This invention addresses this need.

[0006] The priority date of WO2024 / 013394 is prior to the priority date of this application, and the publication date is after the priority date of this application. It discloses solid and semi-solid compositions for administration to ruminants, said solid and semi-solid compositions containing substances capable of inhibiting methane production in ruminants, such as viruses of archaea capable of inhibiting methane production in ruminants. Protection of such compositions is not claimed herein. Summary of the Invention

[0007] In a first aspect of the invention, a virus capable of inhibiting the formation of methane in the human gastrointestinal tract is provided, and a method for using the virus to reduce methane production in a human subject includes administering the virus to the subject.

[0008] In a second aspect of the invention, a pharmaceutical composition is provided comprising a virus capable of inhibiting methane formation in the human gastrointestinal tract. The pharmaceutical composition according to this aspect can be used in a method for reducing methane production in a human subject, the method comprising administering the composition to the subject.

[0009] In a third aspect of the invention, a method for reducing methane production in a human subject is provided, the method comprising administering to the subject a virus capable of inhibiting the formation of methane in the gastrointestinal tract.

[0010] The viruses, pharmaceutical compositions, and methods provided by this invention offer an effective means of reducing methane production in the human body, particularly in C-IBS patients exhibiting elevated methane production levels. Reducing methane production in these patients can alleviate C-IBS-related symptoms, including constipation.

[0011] definition As used in this article, the terms “contains” and “including / includes” mean that at least all of the listed elements must be present, but other elements not mentioned may also be present.

[0012] As used in this article, the term "composed of" means that only the listed elements must exist, such that no other elements not mentioned exist.

[0013] The terms “constipation-predominant irritable bowel syndrome” and “C-IBS” are used interchangeably in this document. They define a subtype of irritable bowel syndrome defined using the Rome IV criteria for irritable bowel syndrome as having abdominal pain for an average of three days per month over the past three months, with hard or lumpy stools accounting for more than 25% of the total stool volume and loose or watery stools accounting for less than 25% of the total stool volume.

[0014] According to the present invention, the term "virus" includes double-stranded or single-stranded RNA or DNA viruses that infect cells of bacteria, archaea, plants, and / or animals.

[0015] As used in this article, the term "archaea" refers to any single-celled prokaryote.

[0016] The term "substrate" according to the present invention should be understood to refer to any solid material on which a virus can be fixed.

[0017] The terms “virus that can inhibit methane production” and “virus” are used interchangeably in this article, referring to a virus that can inhibit methane production in the human body.

[0018] As used herein, the term "about" when applied to one or more values ​​of interest refers to a value similar to the stated reference value. In some embodiments, the term "about" refers to a range of values ​​falling within 25% of the reference value in any direction (greater or less than the reference value). In some embodiments, the term "about" refers to a value falling within a range of 20%, 19%, 18%, 17%, 16%, 15%, 14%, 13%, 12%, 11%, 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, 1% or less of the stated reference value (unless such figures would exceed 100% of the possible value).

[0019] As used herein with respect to a particular pharmaceutical composition, the term "coating" means that a coating is present on at least 10% of the outer surface of the pharmaceutical composition. In some embodiments, the coating is present on at least 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 95% of the outer surface.

[0020] As used herein with respect to the coating of pharmaceutical compositions, the term “encapsulation” means that the pharmaceutical composition is sealed inside the coating (in other words, the pharmaceutical composition is completely contained within the coating).

[0021] As used in this article, “location-controlled release” means the release of the virus at a specific location in the human digestive tract after its administration. Detailed Implementation

[0022] This invention relates to a virus capable of inhibiting the formation of methane in the human gastrointestinal tract, and the virus is used in a method for reducing methane production in the human body.

[0023] The present invention also relates to a pharmaceutical composition comprising a virus capable of reducing methane formation in the human gastrointestinal tract. The pharmaceutical composition may be in the form of a liquid, syrup, capsule, tablet, bead, granule, pellet, sugar tablet, suppository, or pill, preferably a tablet. Even more preferably, the pharmaceutical composition may be in the form of an enteric-coated tablet. The pharmaceutical composition may be used in a method for reducing methane production in a human subject, the method comprising administering the composition to the subject. The pharmaceutical composition preferably also comprises a pharmaceutically acceptable carrier.

[0024] The present invention also relates to a method for reducing methane production in human subjects, the method comprising administering to the subject a virus capable of inhibiting methane production in the gastrointestinal tract.

[0025] In a preferred embodiment, the person suffers from IBS. In a particularly preferred embodiment, the person suffers from C-IBS. This is advantageous because C-IBS patients have particularly high methane production, leading to adverse effects such as constipation. Therefore, reducing methane production in these patients can alleviate these adverse effects.

[0026] The preferred method of administering a virus that can inhibit the production of methane in the gastrointestinal tract is oral or rectal administration, with oral administration being the most preferred method. In this manner, the virus is directly introduced into the gastrointestinal tract, and methane production there is reduced.

[0027] Viruses capable of inhibiting methane production in the gastrointestinal tract can be viruses that interrupt the metabolic pathways of methane production in the gastrointestinal tract, and / or viruses capable of disrupting the gut microbiome. In a preferred embodiment, the virus is an inhibitor of methanogenic bacteria. In a particularly preferred embodiment, the virus is an inhibitor of methanogenic bacteria in the genus *Methanobacterium*. In a particularly preferred embodiment, the virus is an inhibitor of *Methanobacterium spp.* These viruses are particularly effective in reducing methane production in the human body because *Methanobacterium spp.* is a major intestinal methanogen, therefore, administering a virus that inhibits it will be particularly effective in reducing methane production in the human body.

[0028] In a preferred embodiment, the virus capable of inhibiting methane production in the human body is a stabilized virus. For example, the virus is stabilized by immobilization to a substrate as described in EP 1496919 B1. This is advantageous because it ensures that the virus retains its ability to inhibit methane production while also improving its stability relative to free virus.

[0029] In some implementations, such as EP 1496919 B1, the virus is fixed to the substrate via a covalent bond formed between the virus and the substrate.

[0030] In a preferred embodiment, the virus is fixed by its head, leaving its tail free. This ensures the virus retains its activity, as the tail is involved in its ability to recognize and infect specific bacteria and / or archaea. In some embodiments, the virus may be a bacteriophage.

[0031] Advantageously, given that methane production in the gastrointestinal tract is caused by specific prokaryotic methanogens, the use of viruses provides a particularly effective means of delivering targeted disruption of the methane-producing process. Unlike other methane inhibitors that offer less targeted methods and can be toxic to humans, viruses are specific to their target bacteria and / or archaea, and therefore do not produce problematic side effects in humans. Thus, they provide an effective and targeted means of reducing methane production in the human body, and offer a promising approach for alleviating symptoms associated with elevated methane production, such as those experienced by patients with C-IBS.

[0032] In a preferred embodiment, the virus is a bacteriophage that targets bacteria in the gut microbiome. This is advantageous because inhibition of these bacteria will, in turn, negatively impact methane production in the gastrointestinal tract. In another preferred embodiment, the virus is a virus that targets archaea involved in methane production in the human gastrointestinal tract. In a particularly preferred embodiment, the virus is a virus that targets metabolic processes that cause methane production.

[0033] It should be understood that viruses capable of inhibiting methane formation in the human gastrointestinal tract can be isolated by skilled personnel. For example, to isolate viruses targeting archaea, archaeal cultures can be prepared in suitable growth media (such as 119 broth). Liquids can then be collected from suitable viral sources, such as bovine rumen fluid, rumen fecal matter, urban sewage systems, or environmental samples from sources providing habitats for archaea, such as anaerobic soils including peat and peat bogs, and deep-sea hydrothermal vents. The viruses can then be separated from the liquid, concentrated, and purified, for example, by PEG precipitation and ultracentrifugation. The resulting viral suspension can then be inoculated into the archaeal cultures, and the cultures are allowed to grow, thereby initiating the infection and amplification cycle of archaea-specific viruses. These viruses can be filtered from the cultures and repeatedly passaged (i.e., repeating the aforementioned steps with fresh archaea) to obtain pure, viable viruses. Similar procedures can be followed to isolate other viruses.

[0034] Following the procedure described above, a novel virus active against *Methanobacterium brevesii*, having the sequence listed in SEQ ID NO:1, was isolated. The isolation method is described in the examples and... WO2024 / 013394 A1 provides a more detailed description, which is incorporated herein by reference in its entirety. In some embodiments, the nucleic acid capable of inhibiting methane formation in the human gastrointestinal tract contains at least 50% identity with SEQ ID NO:1. In some embodiments, the nucleic acid of the virus capable of inhibiting methane formation in the human gastrointestinal tract contains at least 60% identity with SEQ ID NO:1. In some embodiments, the nucleic acid of the virus capable of inhibiting methane formation in the human gastrointestinal tract contains at least 70% identity with SEQ ID NO:1. In some embodiments, the nucleic acid of the virus capable of inhibiting methane formation in the human gastrointestinal tract contains at least 80% identity with SEQ ID NO:1. In some embodiments, the virus capable of inhibiting methane formation in the human gastrointestinal tract has nucleic acid containing at least 90% identity with SEQ ID NO:1. In some embodiments, the virus capable of inhibiting methane formation in the human gastrointestinal tract has nucleic acid containing at least 95% identity with SEQ ID NO:1. In a particularly preferred embodiment, the virus has the sequence listed in SEQ ID NO:1.

[0035] SEQ ID NO:1: In a preferred embodiment, the pharmaceutical composition of the present invention further comprises at least one other virus capable of inhibiting the production of methane in the human gastrointestinal tract. Similarly, in a preferred embodiment, the method of using the virus and pharmaceutical composition comprises administering at least one other virus capable of inhibiting the production of methane in the human gastrointestinal tract. In a preferred embodiment, the at least one other virus is a virus selected from those disclosed herein that is capable of inhibiting the production of methane in the human gastrointestinal tract. The virus may be stabilized as discussed above.

[0036] It is known that archaea and bacteria develop resistance to specific active substances over time. Therefore, it is advantageous for pharmaceutical compositions and methods to involve mixtures of two or more viruses to minimize the effects of such resistance. The combined use of two or more viruses also offers the additional advantage that, as discussed above, viruses are specific to their target bacteria and / or archaea. Therefore, unlike other methane inhibitors that provide less targeted methods and can cause toxicity to humans, viruses do not cause problematic off-target side effects in humans. Furthermore, using more than one virus reduces the risk that archaea and bacteria have already developed or will develop resistance to the active substance.

[0037] In a preferred embodiment, the pharmaceutical composition of the present invention further comprises at least one other active substance for relieving symptoms of irritable bowel syndrome (IBS). Similarly, in a preferred embodiment, the method of using the virus and pharmaceutical composition includes administering at least one other active substance for relieving symptoms of IBS. In a particularly preferred embodiment, the other active substance is an antispasmodic. Preferably, the antispasmodic comprises scopolamine or a pharmaceutically acceptable salt thereof.

[0038] Co-administration of other active substances that relieve symptoms of irritable bowel syndrome is advantageous because it allows for a more thorough reduction of patient discomfort and symptoms. For example, a patient's constipation can be relieved by administering the virus of this invention, and their abdominal pain can also be attributed to the relief of antispasmodics. This provides a more thorough treatment.

[0039] In some embodiments, the compositions of the present invention further include clay, preferably Fuller's Earth. In some embodiments, the compositions of the present invention also include silica gel. In some embodiments, the compositions of the present invention also include fiber. In some embodiments, the compositions of the present invention also include probiotics. In some embodiments, the compositions of the present invention also include one or more food additives. In some embodiments, the compositions of the present invention also include one or more dietary supplements. In some embodiments, the compositions of the present invention comprise one or more of clay, silica gel, fiber, probiotics, food additives, and dietary supplements.

[0040] In some embodiments, the pharmaceutical compositions of the present invention are configured to provide a location-specific release of the virus into a person. This is advantageous because it allows for targeted treatment of specific parts of the body. For example, the pharmaceutical composition may be configured to provide a location-specific release of the virus when the pharmaceutical composition enters a target release area (such as the small intestine) in a patient's gastrointestinal tract, thus allowing for targeted reduction of methane production in the most problematic parts of the body.

[0041] In some embodiments, this is achieved when the pharmaceutical composition is in the form of an enteric-coated tablet, or more preferably encapsulated in an enteric coating. The enteric coating protects the active ingredient (i.e., the virus) from the acidic pH environment of the patient's stomach, preventing its release. Once the tablet is delivered to the patient's intestines, the coating breaks down, thereby releasing the virus in a targeted manner.

[0042] Example Example 1 Virus active against *Methanobacter schlegelii* was isolated from slaughterhouse samples of fresh bovine rumen fluid, the samples being concentrated as described below by filtration and the addition of polyethylene glycol (PEG) and sodium chloride to a final concentration of 10% (w / v) and 0.5 M, respectively.

[0043] First, viral particles were isolated from rumen fluid, concentrated, and purified using PEG precipitation and centrifugation. The purified viral suspension was then inoculated into archaea cultures in 119 broth, and the cultures were allowed to grow for 48 hours, thereby initiating infection and amplification cycles with any archaea-specific virus.

[0044] Following incubation, methane production was measured using gas chromatography-mass spectrometry (GC-MS). Cultures inoculated with the viral preparation were compared to untreated but otherwise identical cultures. The presence of viable virus was confirmed by a measurable reduction in methane production in cultures exposed to the viral preparation. Virus released during the infection cycle was recovered from the cultures by filtration through a 0.22 μm filter, allowing for the separation of viral particles from the archaea in the culture medium.

[0045] The recovered viral suspension was then used to inoculate fresh cultures of host archaea cells as previously described. This process of infection, replication, extraction, and re-infection (referred to as passage) was repeated four and six times to obtain a virus active against *Methanobacter schrenckii*. The virus active against *Methanobacter schrenckii* is a novel virus having the sequence shown in SEQ ID NO:1.

[0046] The effect of a virus on methane reduction was investigated using fresh human feces obtained from three healthy donors in an established in vitro colon model. This virus had been shown to be active against *Methanobacterium spp.* (ATCC 35061). Since the nature of the archaeal community inherent in each fecal donor sample was unclear, *Methanobacterium spp.* (ATCC 35061) was exogenously added to the in vitro colon model to provide a sensitive target for the virus.

[0047] The in vitro colon model comprises a 100 ml glass container with a sealed rubber cap. The container is acid-washed, sterilized, and airtight, and can be operated in an anaerobic chamber containing a standard anaerobic gas mixture of 80% nitrogen, 10% carbon dioxide, and 10% hydrogen. The rubber cap is self-sealing and remains airtight even after puncture with a fine-needle needle. All materials are degassed and stored under anaerobic conditions in preparation for use in this compartment.

[0048] Feces from each donor were processed individually, and experiments were conducted in duplicate for each case. Each sample was homogenized in sterile degassed PBS buffer to form a fecal slurry. Other materials included sterile degassed 119 DSMZ medium, medium containing planktonic growths of *Methanobacterium spp.*, and virus-containing medium.

[0049] As shown in Table 1, fecal slurry and culture medium, or fecal slurry, *Methanobacterium spp.*, and culture medium were added to the in vitro colon model containers in an anaerobic chamber. Rubber caps were placed on the containers, and they were sealed. Then, a 25G needle, continuously connected to a gas line delivering a mixture of 90% hydrogen and 10% carbon dioxide at 1 bar above atmospheric pressure, was punctured through the seal and delivered to each container for 45 seconds before the needle was withdrawn. Thus, each airtight container in the in vitro colon model contained 20.2 ml of liquid in a hydrogen-rich, oxygen-deficient gas mixture. The containers were incubated at 37°C for 24 hours, after which 1.0 ml of gas was withdrawn via an airtight Hamilton syringe to detect methane, ensuring that all containers contained viable archaeal growth. Using a syringe and a 25G needle inserted into the rubber cap of each sealed container, 1.8 ml of culture medium or 1.8 ml of virus-containing culture medium was added, as shown in Table 1. The container was incubated at 37°C for another 48 hours, after which 1.0 ml of gas was extracted and transferred to a labeled and sealed 10 ml hungate tube for analysis.

[0050] Using an airtight Hamilton syringe, 200 μl of gas was drawn from each labeled Hengette tube and analyzed individually by gas chromatography (GC). The contribution of exogenous *Methanobacterium spp.* was elucidated by subtracting the GC reading of methane produced in the fecal-only control for each fecal sample. After correcting for methane in the fecal-only control, the GC readings of feces + *Methanobacterium spp.* were compared with those of feces + *Methanobacterium spp.* + virus to determine the effect of the virus on methane emissions in an in vitro colonic model.

[0051] The data in Table 2 show that each fecal sample cultured without the addition of *Methanogenic Shorter* produced detectable levels of methane. This indicates that each of the three fecal samples possessed an inherent methanogenic archaea population, and therefore it is inferred that the human donors of these feces carried methanogenic archaea in their gastrointestinal tract. The feces from donors 1 and 2 exhibited the highest and lowest original methanogenic capacity, respectively. As shown in Table 2, the presence of the virus reduced the average GC reading of the fecal samples from each donor. After adjusting for methane emissions caused by the inherent archaea population in the fecal samples, it can be seen that the presence of the virus reduced methane emissions by an average of 12.16% to 26.13% under the experimental conditions.

[0052] It should be understood that the in vitro colon model used in this experiment represents the anatomical and physiological composition of the human colon, where an ingested transport time of up to 72 hours is considered normal. In constipation-predominant irritable bowel syndrome (C-IBS), colonic transport times typically exceed 100 hours. Therefore, it should be further understood that the benefit of the virus to in vivo methane release in the human colon may be far greater than the benefit shown by the in vitro colon model during an incubation period of only 48 hours. Furthermore, the experiment described a scenario where the primary colon was first presented with the virus, thereby inducing an initial infection cycle and lysis of target archaea. With repeated daily administration of the virus (which may be appropriate for C-IBS patients), the contribution of the infection cycle established from previous doses would produce a more comprehensive methane relief effect.

[0053] The disclosed implementation scheme with the number [number] 1. A virus capable of inhibiting the formation of methane in the human gastrointestinal tract, wherein the method of using the virus to reduce methane production in a human subject includes administering the virus to the subject.

[0054] 2. A pharmaceutical composition comprising a virus capable of reducing methane formation in the human gastrointestinal tract.

[0055] 3. The pharmaceutical composition according to embodiment 2, wherein the pharmaceutical composition is in the form of a liquid, syrup, capsule, tablet, bead, granule, pellet, sugar tablet, pill, or suppository.

[0056] 4. The pharmaceutical composition according to embodiment 3, wherein the pharmaceutical composition is in tablet form.

[0057] 5. The pharmaceutical composition according to embodiment 4, wherein the tablet is coated with an enteric coating, preferably wherein the tablet is encapsulated with an enteric coating.

[0058] 6. The pharmaceutical composition of any one of embodiments 2-5, wherein the pharmaceutical composition is configured to release the virus specifically to the person.

[0059] 7. A pharmaceutical composition according to any one of embodiments 2-6, wherein the pharmaceutical composition is used in a method for reducing methane production in a human subject, the method comprising administering the composition to the subject.

[0060] 8. A method for reducing methane production in a human subject, the method comprising administering to the subject a virus capable of inhibiting methane production in the gastrointestinal tract.

[0061] 9. The substance for use according to embodiment 1, the pharmaceutical composition for use according to embodiment 7, or the method according to embodiment 8, wherein the person suffers from irritable bowel syndrome.

[0062] 10. The substance, pharmaceutical composition, or method for use according to embodiment 9, wherein the irritable bowel syndrome is constipation-predominant irritable bowel syndrome.

[0063] 11. The virus, pharmaceutical composition, or method for use as described in any of the foregoing embodiments, wherein the administration is oral or rectal, preferably oral.

[0064] 12. The virus, pharmaceutical composition, or method for use according to any of the foregoing embodiments, wherein the virus inhibits the metabolic pathway of methane production in the human gastrointestinal tract.

[0065] 13. The virus, pharmaceutical composition, or method for use according to any of the foregoing embodiments, wherein the virus is an inhibitor of methanogens, preferably an inhibitor of methanogens in the genus *Bacillus methanogenus*.

[0066] 14. The virus, pharmaceutical composition, or method for use according to any of the foregoing embodiments, wherein the virus is an inhibitor of *Methanobacterium brevei*.

[0067] 15. The virus, pharmaceutical composition, or method for use according to any of the foregoing embodiments, wherein the virus is a virus that targets metabolic processes involved in methane generation.

[0068] 16. The virus, pharmaceutical composition, pharmaceutical composition or method for use according to any of the foregoing embodiments, wherein the virus is stabilized.

[0069] 17. The virus, pharmaceutical composition, or method of use provided according to embodiment 16, wherein the virus is stabilized by immobilization to a substrate.

[0070] 18. A virus, pharmaceutical composition, or method for use according to embodiment 16 or 17, wherein the virus is fixed via its head.

[0071] 19. The pharmaceutical composition or pharmaceutical composition for use according to any of the foregoing embodiments, wherein the composition further comprises at least one other virus capable of inhibiting the production of methane in the human gastrointestinal tract.

[0072] 20. The virus, pharmaceutical composition, or method for use according to any of the foregoing embodiments, wherein the method further comprises administering at least one other virus capable of inhibiting the production of methane in the human gastrointestinal tract.

[0073] 21. The pharmaceutical composition or pharmaceutical composition for use according to any of the foregoing embodiments, wherein the composition further comprises at least one other active substance that relieves the symptoms of irritable bowel syndrome.

[0074] 22. The virus, pharmaceutical composition, or method for use according to any of the foregoing embodiments, wherein the method further comprises administering at least one other active substance that relieves the symptoms of irritable bowel syndrome.

[0075] 23. The virus, pharmaceutical composition, pharmaceutical composition for use, or method for use according to embodiment 21 or 22, wherein the other active substance is an antispasmodic drug.

[0076] 24. The virus, pharmaceutical composition, pharmaceutical composition for use, or method for use according to embodiment 23, wherein the antispasmodic comprises scopolamine or a pharmaceutically acceptable salt thereof.

[0077] 25. The virus, pharmaceutical composition, or method for use according to embodiment 24, wherein the virus is stabilized.

[0078] The foregoing disclosure provides exemplary embodiments of the invention and is not intended to be limiting. It should be understood that various other modifications and variations of the invention are also possible.

Claims

1. A virus capable of inhibiting the formation of methane in the human gastrointestinal tract, a method for reducing methane production in a human subject, the method comprising administering the virus to the subject, wherein the virus is an inhibitor of methanogenic archaea.

2. A method for reducing methane production in a human subject, the method comprising administering to the subject a virus capable of inhibiting methane production in the gastrointestinal tract, wherein the virus is an inhibitor of methanogenic archaea.

3. A pharmaceutical composition comprising a virus capable of reducing methane formation in the human gastrointestinal tract, wherein the pharmaceutical composition is used in a method for reducing methane production in a human subject, the method comprising administering the composition to the subject, wherein the virus is an inhibitor of methanogenic archaea.

4. A pharmaceutical composition comprising a virus capable of reducing methane formation in the human gastrointestinal tract, wherein the virus is an inhibitor of methanogenic archaea and wherein the composition is not a solid or semi-solid composition for administration to ruminants.

5. The pharmaceutical composition of claim 4, wherein the composition is a liquid, syrup, capsule, tablet, or suppository.

6. The pharmaceutical composition for use according to claim 3 or the composition according to claim 4, wherein the composition is in tablet form.

7. The virus for use according to claim 1, the pharmaceutical composition for use according to claim 3 or 6, or the method according to claim 4, wherein the person suffers from irritable bowel syndrome, optionally wherein the irritable bowel syndrome is constipation-predominant irritable bowel syndrome.

8. The virus, pharmaceutical composition, or method for use as described in any of the preceding claims, wherein the administration is oral or rectal, preferably oral.

9. The virus, pharmaceutical composition, or method for use according to any of the preceding claims, wherein the virus is an inhibitor of methanogens in the genus *Biomycobacterium*, optionally wherein the virus is an inhibitor of *Biomycobacterium schrenckii*.

10. The virus, pharmaceutical composition, or method for use according to any of the preceding claims, wherein the virus is stabilized.

11. The virus, pharmaceutical composition, or method of use according to claim 10, wherein the virus is stabilized by immobilization to a substrate.

12. A pharmaceutical composition or pharmaceutical composition for use according to any of the preceding claims, wherein the composition further comprises at least one other virus capable of inhibiting the production of methane in the human gastrointestinal tract.

13. The virus, pharmaceutical composition, or method for use according to any of the preceding claims, wherein the method further comprises administering at least one other virus capable of inhibiting the production of methane in the human gastrointestinal tract.

14. A pharmaceutical composition, drug composition, virus, or method for use according to any of the preceding claims, wherein the composition further comprises at least one other active substance that relieves symptoms of irritable bowel syndrome, optionally wherein said other active substance is an antispasmodic agent; or The method further includes administering at least one other active substance that relieves the symptoms of irritable bowel syndrome, optionally said other active substance being an antispasmodic drug.

15. The virus, pharmaceutical composition, pharmaceutical composition for use, or method for use according to claim 14, wherein the antispasmodic comprises scopolamine or a pharmaceutically acceptable salt thereof.

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