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Content archived on 2024-06-18

Production and delivery of antibody fragments against gastrointestinal pathogens by lactobacilli

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Foods that fight stomach bugs

Every year diseases of the stomach and intestines cause an estimated 2 million deaths around the world. As effective treatments are often still lacking, scientists have developed a solution using human gut bacteria.

Lactobacilli are microbes found naturally in the gastrointestinal (GI) tract of humans. They have been genetically engineered to produce antibodies against human diseases and could help the body's immune system fight GI infections. The EU-funded LACTOBODY (Production and delivery of antibody fragments against gastrointestinal pathogens by lactobacilli) project has modified Lactobacilli so that they carry antibody fragments against major enteric disease causing microbes. Researchers first isolated parts of antibodies that target two severe diarrhoea-causing agents: rotavirus and the toxins of Clostridium difficile. The lactobacilli were then genetically modified to produce these antibody fragments. A lead fragment against rotavirus, variable domains of camelid heavy chain-only (VHH), called ARP1, was tested in a community-based, double-blind placebo controlled interventional trial in south India. Produced in yeast, a large batch could be prophylactically administered to children. In parallel, the researchers generated, selected and expressed new VHH and single-chain variable fragments against the gastrointestinal pathogens rotavirus and C. difficile in lactobacilli. The modified bacteria were tested for their protective capacity in vitro and in animal models. The project has had success in the scientific community, with seven journal publications, three in preparation with another three expected in the imminent future. LACTOBODY research results were presented at international meetings and two patent applications have been filed. LACTOBODY project results could lead to the development of a new functional food that can either act as a prophylactic or as therapy against GI infections. As well as passive administration, introduction of these antibodies into the intestine of vulnerable groups is an efficient and cheap alternative to existing therapies. Of benefit, particularly in young children, those suffering from malnutrition or immunodeficiency and ageing people, they could also help prevent hospital infections. Novel functional foods that can reduce infectious diarrhoea have vast market opportunities. Moreover, if lactobodies prove successful at inducing passive immunity, they could open the door for therapies against many other human and animal enteric diseases.

Keywords

Functional food, stomach bug, antibodies, GI, LACTOBODY

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