Study protocol for a randomised controlled trial evaluating the efficacy of dietary modulation of probiotics on nutritional status and antibody response to SARS-CoV-2 in Indonesian adolescents: gut-lung axis (DIVINE).

Abstract

During the pandemic, overweight and obese adolescents were at a higher risk of COVID-19 infection. Indonesia's government has implemented prevention programmes and immunisation; however, the rise in SARS-CoV-2 infections among adolescents is exacerbated by low-quality diet and lifestyle habits. Also, the vaccine programme is not prioritised in this population. To address this, a solution involves providing probiotics and counselling on healthy lifestyle habits to improve diet and immunity. Therefore, we designed a protocol for a randomised controlled trial with a 20-week intervention to investigate the effect of probiotics supplementation and counselling on healthy lifestyle habits, including healthy eating and physical activity, and psychosocial stimulation, on nutritional status and antibody response against SARS-CoV-2 in this group. This clinical trial aims to investigate the effects of probiotic supplementation on healthy overweight and obese adolescents. The study will involve 440 adolescents aged 12-17 living in Jakarta, Surabaya or Yogyakarta for at least 6 months and have completed at least two doses of the COVID-19 vaccine. The intervention group will receive daily probiotic supplementation of three strains, including <i>Bifidobacterium animalis</i> subsp. <i>Lactis</i> (BB-12), <i>Lactobacillus acidophilus</i> (LA-5) and <i>Lactobacillus rhamnosus</i> (LGG), at the level of 10⁹-10¹⁰ colony-forming units for 20 weeks, while the control group will receive a placebo. Both groups will receive weekly counselling on healthy eating habits, physical activity and psychosocial stimulation. The primary outcomes will be changes in the body mass index for age z-score and IgG specific to SARS-CoV-2 titre concentrations between groups. The secondary outcomes will include changes in secretory IgA specific to SARS-CoV-2 titre concentrations, monoclonal antibodies against SARS-CoV-2 spike protein, gut microbiota diversity and the score of Healthy Eating Index 2015. The study protocol was approved by the Ethics Committee of the Faculty of Medicine, Universitas Indonesia-Cipto Mangunkusumo Hospital (KET 763/UN2.F1/ETIK/PPM.00.02/2022: 1 August 2022). The study results will be disseminated in open-access international journals, scientific meetings and conferences with stakeholders. The study has been registered at https://clinicaltrials.gov with identifier number NCT05623007.