Human milk products in the National Health Service: a cross-sectional survey of use and industry contact across England's trusts.

Objectives: Commentators and professional organisations note that an expanding market in human milk-based products (HMBPs) could reduce breastfeeding, compromising maternal and infant health, and undermine public milk bank donations. We investigate whether English NHS trusts purchased these products and whether HMBP companies have marketed to them. Design: Freedom of Information (FOI) requests asking: (1) whether trusts obtained human milk; (2) if so, how; and (3) whether HMBP companies had approached them. We analysed trusts' responses qualitatively. In 2023, an FOI request to the Food Standards Authority (FSA) following a product recall. Setting: England. Participants: One hundred and ninety-four NHS trusts, the FSA. Main Outcome Measures: Obtaining human milk, approaches by companies, and trust responses to approaches. Results: One hundred and seventy-six trusts responded, 102 reporting human milk from milk banks. No trusts reported purchasing from companies in 2022. In 2023, the FSA confirmed six English hospitals used HMBPs from one company; an FOI for trusts' names was refused on law enforcement grounds. Two trusts reported participating in clinical trials funded by companies. Twenty-one reported approaches, using several strategies, including uninvited ward visits. Trusts rejected marketing based on guidance from: (1) trust dieticians or physicians; (2) regional regulatory bodies; (3) professional bodies; and (4) perceived application of an International Code on breastfeeding. Conclusions: Companies market to trusts, adopting methods previously used by the formula industry. Trusts express confusion over whether this infringes agreements designed to promote breastfeeding. We encourage clarification and guidance for professionals and trusts to ensure safety, infant and maternal health, and protect public provision.

The effect of interventions targeting gut microbiota on depressive symptoms: a systematic review and meta-analysis.

BACKGROUND: Despite their popularity, the efficacy of interventions targeting gut microbiota to improve depressive symptoms is unknown. Our objective is to summarize the effect of microbiome-targeting interventions on depressive symptoms. METHODS: We conducted a systematic review and meta-analysis. We searched MEDLINE, Embase, PsycINFO, Database of Abstracts of Reviews of Effects, Cochrane Database of Systematic Reviews and the Cochrane Controlled Register of Trials from inception to Mar. 5, 2021. We included studies that evaluated probiotic, prebiotic, synbiotic, paraprobiotic or fecal microbiota transplant interventions in an adult population (age ≥ 18 yr) with an inactive or placebo comparator (defined by the absence of active intervention). Studies must have measured depressive symptoms with a validated scale, and used a randomized controlled trial study design. We conducted a random effects meta-analysis of change scores, using standardized mean difference as the measure of effect. RESULTS: Sixty-two studies formed the final data set, with 50 included in the meta-analysis. Probiotic, prebiotic, and synbiotic interventions on depressive symptoms showed statistically significant benefits. In the single studies evaluating each of fecal microbiota transplant and paraprobiotic interventions, neither showed a statistically significant benefit. INTERPRETATION: Despite promising findings of benefit of probiotic, prebiotic and synbiotic interventions for depressive symptoms in study populations, there is not yet strong enough evidence to favour inclusion of these interventions in treatment guidelines for depression. Critical questions about species administered, dosage and timing relative to other antidepressant medications remain to be answered. STUDY REGISTRATION: PROSPERO no. 143178.

The safety and efficacy of fecal microbiota transplantation in a population with bipolar disorder during depressive episodes: study protocol for a pilot randomized controlled trial.

BACKGROUND: Bipolar disorder (BD) is a chronic, debilitating illness with significant medical morbidity, often secondary to current treatments, and a high recurrence rate. This burden of disease reflects limitations in the tolerability and efficacy of current treatments. There is a compelling body of evidence linking the gut microbiota to mental illness, and while microbial manipulation via probiotic use has been studied as a therapeutic in BD, targeted trials of fecal microbiota transplantation (FMT) have not been conducted in this population. METHODS AND DESIGN: We describe a pilot randomized controlled trial of FMT in participants with BD depression to assess the feasibility, efficacy, safety, and tolerability of this intervention. Individuals between 18 and 65 years of age will be enrolled in the study if they meet diagnostic criteria for a major depressive episode of at least moderate severity in the context of a BD diagnosis and have not responded to treatment for BD. Participants will be randomized 1:1 to receive either screened and processed donor stool (allogenic FMT) or their own stool (autologous FMT) via colonoscopy and monitored for 24 weeks post intervention. Depressive and manic symptoms, treatment acceptability, and gastrointestinal and other side effects are assessed at baseline (prior to randomization) and weekly. Stool samples to assess microbiome composition are obtained at baseline and 3 and 6 months. DISCUSSION: Currently, FMT represents a novel therapeutic option for treating BD depression. This protocol allows for the assessment of the feasibility, efficacy, acceptability, and safety of an intervention aimed at changing the microbiome in those with BD. Results from this pilot study will guide the development of larger trials of FMT for BD depression and may give more insight into how the gut microbiome are altered in those with BD depression. TRIAL REGISTRATION: Clinical Trials Gov NCT03279224.

Microbiome-derived inosine modulates response to checkpoint inhibitor immunotherapy.

Several species of intestinal bacteria have been associated with enhanced efficacy of checkpoint blockade immunotherapy, but the underlying mechanisms by which the microbiome enhances antitumor immunity are unclear. In this study, we isolated three bacterial species-Bifidobacterium pseudolongum, Lactobacillus johnsonii, and Olsenella species-that significantly enhanced efficacy of immune checkpoint inhibitors in four mouse models of cancer. We found that intestinal B. pseudolongum modulated enhanced immunotherapy response through production of the metabolite inosine. Decreased gut barrier function induced by immunotherapy increased systemic translocation of inosine and activated antitumor T cells. The effect of inosine was dependent on T cell expression of the adenosine A2A receptor and required costimulation. Collectively, our study identifies a previously unknown microbial metabolite immune pathway activated by immunotherapy that may be exploited to develop microbial-based adjuvant therapies.