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One of the less-known problems of obesity is that obese mothers are 50% more likely than those of normal weight to give birth to children who go on to develop autism. This correlation is perplexing, but some suspect it is connected to differences between the gut bacteria of the overweight and of those who are not. One researcher who thinks this way is Mauro Costa-Mattioli of Baylor College of Medicine, in Houston. He has just published evidence in Cell that, in mice at least, a clear relationship does exist between gut flora, obesity and social behaviour. What is particularly intriguing is that the culprit seems to be a single bacterial species.
Dr Costa-Mattioli and his colleague Shelly Buffington set up a series of experiments, each of which involved feeding 100 female mice a normal diet or a high-fat diet for eight weeks, getting those mice pregnant and then examining both the behaviour and the gut flora of their offspring. To monitor behaviour, the researchers put the pups through tests that measured how long they spent interacting with strangers and with inanimate objects. To study the gut floras, they used a test called ribosomal-RNA sequencing to identify which species the animals’ faeces contained.
Dr Costa-Mattioli and Dr Buffington found that the offspring of mothers on the high-fat diet (which made these mothers obese), tended to have problems socialising. On average they interacted with other mice for only 22 seconds during a ten-minute test. Offspring of normal-weight mothers, by contrast, interacted for an average of two minutes. Similarly, when pups were given a choice of interacting with another mouse or with an empty cup, 55% of the offspring of obese mothers preferred the cup. All the pups of normal-weight mothers preferred the company of their fellow rodents.
As expected, the gut bacteria of the obese mothers and their offspring were quite different from, and less diverse than, those of other mice. The researchers’ question was whether restoring a normal set of bacteria to the pups of obese mothers might improve their behaviour. To do this, they took advantage of a tendency mice have to eat each others’ faeces. By housing the offspring of obese mothers with those of normal mothers, they thus reset to normal the gut floras of the pups. That done, they found the pups’ social interactions developed normally, too.
The socialiser
This is an extraordinary result. It suggests that a mouse’s gut bacteria are regulating its behaviour. And further investigation showed how. A close examination of which species are missing from the guts of obese mice and their offspring flagged up one in particular, Lactobacillus reuteri (pictured), which was nine times more abundant in the pups of normal mothers than in those of obese mothers. This, the researchers felt, was worth investigating because L. reuteri was shown, three years ago, to promote the release of oxytocin, a hormone that plays an important role in controlling mammalian social behaviour.
The next experiment was therefore obvious. Dr Costa-Mattioli and Dr Buffington added L. reuteri to the drinking water of both sorts of mouse pup. As controls, they gave similar pups either pure water or water that had heat-killed L. reuteri in it.
Among the offspring of obese mothers, those given the live bacteria developed normally while the control mice developed social problems. This suggested L. reuteri does indeed promote the release of oxytocin in the developing brain, which then helps mice to develop normal social behaviour. To reinforce their case, the investigators dissected the brains of the animals involved in the last experiment and counted up the number of oxytocin-producing cells therein. As they suspected, offspring of obese mothers that were in the control arms of the experiment had 29% fewer such cells than did offspring of normal mothers. Those given L. reuteri in their water, by contrast, had only 13% fewer. That, apparently, was enough to abolish detectable behavioural differences.
Whether L. reuteri plays anything like a similar role in human beings is unknown. But this research suggests it would be well worth looking into. Lack of interest in social interaction, of the sort displayed by the mice Dr Costa-Mattioli and Dr Buffington have been studying, is certainly symptomatic of human autism. If examining the gut floras of autistic children and their mothers (whether or not those mothers are obese) even hinted at something homologous happening in human beings, then dosing infants who might be at risk with L. reuteri could be a sensible idea.
Dr Costa-Mattioli and his colleague Shelly Buffington set up a series of experiments, each of which involved feeding 100 female mice a normal diet or a high-fat diet for eight weeks, getting those mice pregnant and then examining both the behaviour and the gut flora of their offspring. To monitor behaviour, the researchers put the pups through tests that measured how long they spent interacting with strangers and with inanimate objects. To study the gut floras, they used a test called ribosomal-RNA sequencing to identify which species the animals’ faeces contained.
Dr Costa-Mattioli and Dr Buffington found that the offspring of mothers on the high-fat diet (which made these mothers obese), tended to have problems socialising. On average they interacted with other mice for only 22 seconds during a ten-minute test. Offspring of normal-weight mothers, by contrast, interacted for an average of two minutes. Similarly, when pups were given a choice of interacting with another mouse or with an empty cup, 55% of the offspring of obese mothers preferred the cup. All the pups of normal-weight mothers preferred the company of their fellow rodents.
As expected, the gut bacteria of the obese mothers and their offspring were quite different from, and less diverse than, those of other mice. The researchers’ question was whether restoring a normal set of bacteria to the pups of obese mothers might improve their behaviour. To do this, they took advantage of a tendency mice have to eat each others’ faeces. By housing the offspring of obese mothers with those of normal mothers, they thus reset to normal the gut floras of the pups. That done, they found the pups’ social interactions developed normally, too.
The socialiser
This is an extraordinary result. It suggests that a mouse’s gut bacteria are regulating its behaviour. And further investigation showed how. A close examination of which species are missing from the guts of obese mice and their offspring flagged up one in particular, Lactobacillus reuteri (pictured), which was nine times more abundant in the pups of normal mothers than in those of obese mothers. This, the researchers felt, was worth investigating because L. reuteri was shown, three years ago, to promote the release of oxytocin, a hormone that plays an important role in controlling mammalian social behaviour.
The next experiment was therefore obvious. Dr Costa-Mattioli and Dr Buffington added L. reuteri to the drinking water of both sorts of mouse pup. As controls, they gave similar pups either pure water or water that had heat-killed L. reuteri in it.
Among the offspring of obese mothers, those given the live bacteria developed normally while the control mice developed social problems. This suggested L. reuteri does indeed promote the release of oxytocin in the developing brain, which then helps mice to develop normal social behaviour. To reinforce their case, the investigators dissected the brains of the animals involved in the last experiment and counted up the number of oxytocin-producing cells therein. As they suspected, offspring of obese mothers that were in the control arms of the experiment had 29% fewer such cells than did offspring of normal mothers. Those given L. reuteri in their water, by contrast, had only 13% fewer. That, apparently, was enough to abolish detectable behavioural differences.
Whether L. reuteri plays anything like a similar role in human beings is unknown. But this research suggests it would be well worth looking into. Lack of interest in social interaction, of the sort displayed by the mice Dr Costa-Mattioli and Dr Buffington have been studying, is certainly symptomatic of human autism. If examining the gut floras of autistic children and their mothers (whether or not those mothers are obese) even hinted at something homologous happening in human beings, then dosing infants who might be at risk with L. reuteri could be a sensible idea.
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