Both intermittent fasting and specific probiotics have shown promise in improving glucose tolerance with a potential for synergistic effects through alterations to gut microbiota. In this randomized, double-blinded, two-arm feasibility study, we investigated whether intermittent fasting, supplemented with Lacticaseibacillus rhamnosus HN001 probiotic, reduces HbA1c in individuals with prediabetes. All participants with HbA1c 40–50 mmol/mol commenced intermittent fasting (2 days per week of calorie restriction to 600–650 kcal/day) and were randomized 1:1 to either daily probiotic (Lacticaseibacillus rhamnosus HN001) or placebo for 12 weeks. The primary outcome was a change in HbA1c. Secondary outcomes included changes in anthropometry, body composition, glucoregulatory markers, lipids, hunger hormones, liver enzymes, inflammatory markers, gut hormones, calorie and macronutrient intake, quality of life, hunger, mood and eating behavior. Of 33 participants who commenced the trial, 26 participants (mean age 52 years, body mass index (BMI) 34.7 kg/m2) completed the intervention (n = 11 placebo, n = 15 probiotic). HbA1c decreased from 43 ± 2.7 mmol/mol to 41 ± 2.3 mmol/mol, p < 0.001, with average of 5% weight loss. No significant between-group differences were seen in primary or secondary outcomes except for social functioning (p = 0.050) and mental health (p = 0.007) scores as improvements were seen in the probiotic group, but not in the placebo group. This study shows additional psychological benefits of probiotic supplementation during intermittent fasting to achieve weight loss and glycemic improvement in prediabetes.

Aims This meta-analysis aimed to investigate the role of glucagon suppression in regulating glucose homeostasis following diet or bariatric surgery. Methods A comprehensive search of intervention and observational studies was conducted in Medline, Scopus, Web of Science, PubMed and Embase. Random effects model meta-analysis was performed. Primary outcomes were (i) body weight change, (ii) fasting glucagon, (iii) fasting glucose and (iv) fasting insulin concentrations. Results Twenty articles reporting data from 29 interventions were eligible for analysis. Bariatric surgery caused greater weight loss than diet (bariatric -29.7 kg [CI:-36.8, -22.6]; diet -5.8 kg [CI: -8.4, -3.3]; P < 0.00001), an effect that remained significant after adjusting for study duration (P < 0.05). Mean fasting glucagon decreased in parallel with weight loss (-11.8 ng/L [CI: -15.9, -7.8]; P < 0.00001) with no difference between bariatric and diet intervention. Both fasting glucose, and insulin decreased following weight loss (both P < 0.00001; glucose -1.7 mmol/L [CI: -2.0, -1.3]; insulin -50.6 pmol/L [CI: -66.5, -34.7] with greater decrease in fasting insulin between bariatric versus diet (P = 0.01). Conclusions Synergistic suppression of fasting glucagon and insulin resistance may act together to restore normoglycaemia following weight loss. Whether suppression of plasma glucagon may contribute to increased hunger after weight loss and gradual weight regain is not yet known.

ObjectiveWe investigated the potential feasibility of a randomized controlled trial of a nutritional intervention that may alter human gut microbiota and support immune defence against respiratory tract infection in adults (Proposed Study).MethodsIn total, 125 healthy adults aged 18–64 participated in a 6‐month study that measured antibody response to the seasonal trivalent influenza vaccine. We assessed completion rates, procedure adherence rates and the influence of possible exclusion criteria on potential recruitment into the Proposed Study. We examined whether the gut microbiota could be categorised into enterotypes, and whether there was an association between enterotypes and the antibody response to the influenza vaccine.ResultsThe participant completion rate was 97.6% (95% CI 93.1–99.5%). The proportions (95% CI) of participants who may be excluded for antibiotic or corticosteroid use in the 30 days prior to the study, or due to receiving the influenza vaccine in the previous two years were 9.6% (5.1–16.2), 8.0% (3.9–14.2) and 61.6% (52.5–70.2), respectively. All participants were stratified into four gut microbiota enterotypes. There was no association between these enterotypes and the antibody response to the influenza vaccine, although the study was not powered for this outcome.ConclusionThis study design is suitable for the Proposed Study. The completion rate is likely to be high, although exclusion criteria should be selected with care. Further analyses of gut microbiota composition or function in association with antibody and immune responses are warranted to explore the role of host–microbiota interactions on protective immunity.

Long-term weight loss maintenance is often difficult to achieve. This review analysed qualitative data on self-perceived barriers and facilitators of weight loss and weight loss maintenance among weight loss intervention participants. A literature search was conducted using electronic databases. Qualitative studies written in English and published between 2011–2021 were eligible for inclusion if they explored the perspectives and experiences of individuals who received standardised dietary and behavioural support for weight loss. Studies were excluded if weight loss was achieved through self-directed methods, only increasing physical activity, or surgical or pharmacological interventions. Fourteen studies were included, totaling 501 participants from six countries. Thematic analysis was used to identify four aggregate themes: internal factors (i.e., motivation and self-efficacy), programme-specific factors (i.e., the intervention diet), social factors (i.e., supporters and saboteurs), and environmental factors (i.e., an obesogenic environment). Our findings demonstrate that internal, social, and environmental factors all influence weight loss success, as well as the acceptability of the weight loss intervention. Future interventions may be more successful if they prioritise participant acceptability and engagement by, for example, providing tailored interventions, a structured relapse management plan, strategies to enhance autonomous motivation and emotional self-regulation, and extended contact during weight loss maintenance.

Influenza vaccination is an effective public health measure to reduce the risk of influenza illness, particularly when the vaccine is well matched to circulating strains. Notwithstanding, the efficacy of influenza vaccination varies greatly among vaccinees due to largely unknown immunological determinants, thereby dampening population-wide protection. Here, we report that dietary fibre may play a significant role in humoral vaccine responses. We found dietary fibre intake and the abundance of fibre-fermenting intestinal bacteria to be positively correlated with humoral influenza vaccine-specific immune responses in human vaccinees, albeit without reaching statistical significance. Importantly, this correlation was largely driven by first-time vaccinees; prior influenza vaccination negatively correlated with vaccine immunogenicity. In support of these observations, dietary fibre consumption significantly enhanced humoral influenza vaccine responses in mice, where the effect was mechanistically linked to short-chain fatty acids, the bacterial fermentation product of dietary fibre. Overall, these findings may bear significant importance for emerging infectious agents, such as COVID-19, and associated de novo vaccinations.

IntroductionPharmaceutical drugs are beneficial to inflammatory conditions but with side effects, which led to the search for alternative therapies. Perna canaliculus, the New Zealand green-lipped mussel, have shown promise in placebo-controlled trials for inflammatory conditions. Fucoidan, an extract from seaweed Undaria pinnatifida, has been found to have beneficial effects on joint pain and insulin resistance. However, green-lipped mussel and fucoidan have never been combined.Methods and analysisA parallel, two-arm, double-blind, randomized, placebo-controlled trial will be conducted in New Zealand to determine whether a food product supplemented with green-lipped mussel and fucoidan improves joint pain and/or insulin resistance. Those who are ethnically Chinese, are aged over 30 years, have prediabetes and hip or knee joint pain will be eligible to participate. They will be randomized at 1:1 ratio to consume either dark chocolate supplemented with 1000 mg mussel powder and 1000 mg fucoidan or dark chocolate with no active substances daily for 100 days. The primary endpoints are change in insulin resistance and patient-reported joint pain. Secondary endpoints include anthropometry, fasting glucose and insulin, HbA1c, inflammatory markers, satiety, quality of life, physical function, pain intensity, and analgesic medication use. A sample size of 150 (75 per arm) will provide 90% power at an overall significance level of 5% (two-sided) to detect a standardized effect size of 0.625 on either of the two co-primary outcomes allowing for 10% loss.Ethics and disseminationThe study was approved by the Health and Disability Ethics Committee (number: 20/STH/153). Results will be made available to participants, funders, and other researchers.DiscussionThis trial will provide data on the potential utility of a mussel-fucoidan supplement in reducing joint pain and/or insulin resistance, to inform the development of a supplemented food product suitable for the Chinese market.Clinical trial registrationhttps://trialsearch.who.int/Trial2.aspx?TrialID=ACTRN12621000413820, ANZCTR Registration: ACTRN12621000413820, on 15 April 2021.

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