A Real-world Study of Gastrointestinal Health and Mental Wellness in U.S. Adults Following 12 Weeks of Probiotic Supplementation.

• Probiotic (Dietary supplement): Two capsules to be self-administered orally once daily, each containing 5 x 10\^9 colony-forming units (CFU) of Bifidobacterium longum (1714™) and Bifidobacterium longum (35624™) combined, equating to a total daily probiotic dose of 1 x 10\^10 CFU, for 12 weeks.

Primary outcomes

• Mean change in PROMIS Belly Pain 5a T-score [From baseline to end of week 12]: Data collection time-points: Weeks 0 (Baseline), 4, 8, 12, 16

Secondary outcomes

• Mean change in PROMIS Diarrhea 6a T-score [From baseline to end of week 12]: Data collection time-points: Weeks 0 (Baseline), 4, 8, 12, 16
• Mean change in PROMIS Constipation 9a T-score [From baseline to end of week 12]: Data collection time-points: Weeks 0 (Baseline), 4, 8, 12, 16
• Mean change in PROMIS Gas and Bloating 13a (v1.1) T-score [From baseline to end of week 12]: Data collection time-points: Weeks 0 (Baseline), 4, 8, 12, 16
• Mean change in PROMIS Emotional Distress - Anxiety 6a T-score [From baseline to end of week 12]: Data collection time-points: Weeks 0 (Baseline), 4, 8, 12, 16
• Mean change in PROMIS Fatigue 6a T-score [From baseline to end of week 12]: Data collection time-points: Weeks 0 (Baseline), 4, 8, 12, 16
• Mean change in PROMIS Sleep Disturbance 6a T-score [From baseline to end of week 12]: Data collection time-points: Weeks 0 (Baseline), 4, 8, 12, 16
• Mean change in PROMIS Cognitive Function 8a (v2.0) T-score [From baseline to end of week 12]: Data collection time-points: Weeks 0 (Baseline), 4, 8, 12, 16
• Mean change in Visual Analogue Mood Scale (VAMS) score [From baseline to end of week 12]: Data collection time-points: Weeks 0 (Baseline), 4, 8, 12, 16
• Mean change in self-reported dietary behaviours [From baseline to end of week 12]: Data collection time-points: Weeks 0 (Baseline), 4, 8, 12, 16
• GI symptom responder rate, defined as a participant achieving a ≥5-point reduction in T-score from baseline to week 12 in PROMIS T-scores for Belly Pain 5a [At end of week 12]
• Mood responder rate, defined as a participant achieving a ≥20% improvement in VAMS score from baseline to week 12 [At the end of week 12]

Other outcomes

• Mean changes during probiotic wash-out in PROMIS T-scores (all GI and psychosocial domains respectively) [From end of week 12 to end of week 16]: Data collection time-points: Weeks 0 (Baseline), 4, 8, 12, 16
• Mean changes during probiotic wash-out in Visual Analogue Mood Scale (VAMS) score [From end of week 12 to end of week 16]: Data collection time-points: Weeks 0 (Baseline), 4, 8, 12, 16
• Mean changes during probiotic wash-out in self-reported dietary behaviours [From end of week 12 to end of week 16]: Data collection time-points: Weeks 0 (Baseline), 4, 8, 12, 16
• Mean change in cortisol awakening response, as measured using salivary cortisol samples [From baseline to end of week 4]
• Study product compliance, as measured by self-reported daily intake [From baseline to end of week 12]
• Incidence of adverse events [From baseline to end of week 16]: Data collection time-points: Weeks 0 (Baseline) and 4

Sex: All, ages: 18 Years to any, accepts healthy volunteers

Inclusion Criteria:

* Females or males at least 18 years of age at the planned start date.
* Reporting mild-to-moderate GI symptoms at screening, defined as recurrent abdominal pain or discomfort at least 3 days per month on average in the last 3 months, associated with bowel movement (either improvement or exacerbation), and a change in the form and/or frequency of bowel movements, with initial onset of symptoms at least 6 months ago. An adaptive design will allow recruitment of participants with initial onset of at least 3 months ago, in case of recruitment delays.
* Owner of a personal smartphone which: (i) only they have access to, and (ii) has Apple AppStore or Android store access to the free-to-use Trialflare app.
* Willing to:

  * Consume the dietary supplement daily for the duration of the study
  * Collect salivary samples according to instructions at baseline and week 4
  * Complete other study assessments digitally

Exclusion Criteria:

Individuals meeting any of the following criteria will be excluded:

* Pregnant, breastfeeding, or planning pregnancy during the study period
* Known allergy or intolerance to any component of the study product
* Presence of a significant medical, gastrointestinal, neurological, or psychiatric condition which, in the opinion of the Principal Investigator (PI), may pose a safety risk to the participant or interfere with interpretation of the study results. Conditions considered during eligibility assessment include, but are not limited to:

  * Coeliac disease
  * Inflammatory bowel disease (IBD), including Crohn's disease or ulcerative colitis
  * Gastrointestinal cancer
  * Previous removal of part of the bowel (bowel resection), or presence of a colostomy or ileostomy
  * Other significant gastrointestinal conditions
  * Significant neurological or neurodegenerative conditions (for example Parkinson's disease, motor neurone disease or Alzheimer's disease)
  * Major psychiatric illness requiring hospital admission within the past 12 months, or currently unstable psychiatric treatment Final eligibility determination will remain at the discretion of the Principal Investigator, taking into consideration the participant's current health status, treatment history, and suitability for participation.
* Current or recent (within the last 1 month) use of:

  * Antibiotics
  * Other probiotic products
  * Supplements intended to affect GI health, mood, sleep, stress, or anxiety
* Current use of a GLP-1 receptor agonist medication where the participant has not been receiving a stable dose for at least 8 weeks prior to enrolment, or where a dose change is anticipated during the study period.
* Participation in another clinical or nutritional study that could interfere with this study, any other condition or circumstance which, in the opinion of the PI, may make the participant unsuitable for the study, including concerns regarding compliance with study procedures or reliability of data submission.

• Katy Sorensen, MSc, Study director, Novonesis
• Eamonn MM Quigley, MD, Principal investigator, Underwood Center for Digestive Health, Houston Methodist Hospital