An Intervention Study Using HMOs to Improve IBS Symptoms - Trial NCT06281600

Timeline & Enrollment

Primary Outcome

IBS-SSS

Summary

There is now strong evidence implicating the human gut microbiota in many gastrointestinal
 diseases, including irritable bowel syndrome (IBS). Importantly, this enteric population is
 susceptible to dietary intervention and represents an exciting target for the prevention and
 treatment of gut mediated disorders. This study will investigate microbial components and
 activities associated with the gut microbiome, using a global systems biology approach to
 explore the capacity of a human milk carbohydrate intervention in modulating this microbial
 community to target IBS, with the primary objective of improving IBS symptoms.
 
 IBS is a highly prevalent gastrointestinal (GI) disorder with significant negative impact on
 quality of life of patients and high healthcare costs. Although prognosis of IBS is benign,
 it is a disorder that poses a considerable burden on the individual sufferer and society.
 Patients typically present with chronic abdominal pain and an altered bowel habit, frequently
 accompanied by bloating and distension. Often, IBS will afflict sufferers for life, with
 flares of activity followed by periods of remission. Incidence commonly peaks in the third
 and fourth decades of life.
 
 IBS is suggested to be a disorder of gut-brain interaction, and alterations of the
 microbiota-host interactions at the mucosal border may cause symptoms such as those
 previously mentioned. Therefore, microbiota-targeted interventions may benefit some people
 with IBS by beneficially modulating the gut microbiome. Several studies have confirmed that
 prebiotics, such as galactooligosaccharides (GOS), are able to successfully stimulate gut
 bifidobacteria and alleviate symptoms in IBS. Prebiotics are defined as a substrate that is
 selectively utilised by host microorganisms conferring a health benefit [8]. These studies
 suggest that prebiotics may have potential as therapeutic agents in IBS.
 
 Breastmilk is known to play a crucial role in the development of infants, providing key
 nutrients and immunological compounds important for initial protection against pathogens [9].
 Among these compounds, human milk oligosaccharides (HMOs) represent the third most important
 component of breastmilk after lipids and lactose. HMOs have also been investigated for
 potential health benefits in adults, including their potential role as prebiotics for
 improved gut microbiota modulation.
 
 Studies looking specifically at HMO interventions in humans with IBS are sparse. These
 include a phase II, parallel, RCT in 58 IBS volunteers by Iribarren et al. and an open-label
 trial with 245 IBS participants from 17 sites across USA by Palsson et al.. None have been
 sufficiently powered to a degree which could influence clinical practice, but crucially
 tolerability and safety profiles of HMOs investigated, to date, have been consistently high.
 
 Using the global systems biology approach not yet applied to this research question, a
 pre-competitive approach to selecting a candidate HMO, and a crossover feasibility trial
 design, the investigators hope to forge a new direction in establishing the merits of HMO use
 in IBS.
 
 This study will look specifically at patients with all IBS subtypes, an area where there is a
 real therapeutic gap and clinical need for safe, effective therapy to improve quality of
 life. Participants will be randomly allocated to be given either the HMO or a placebo, with
 neither the patient nor the researchers knowing which they are receiving (randomised and
 double blind design). They will take this HMO or placebo for 28 days (randomly distributed),
 and then stop taking it in a 'washout' period of 28 days, allowing the gut microbiota to
 return to baseline. Then, the participants will take the other intervention (placebo or
 prebiotic, whichever they did not take in the first half of the study) for 28 days, then have
 a further washout period of 14 days. The study will then be over.
 
 With this proposal, the aim is to explore how HMOs affect the gut microbiota and whether they
 can do so in a manner that positively influences patients with IBS. The investigators also
 hope to develop molecular profiling as part of a research toolkit for gut microbiome-based
 HMO supplement studies.

ICD-10 Classifications