Secrets of the Human Body. Andrew Cohen

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СКАЧАТЬ from other species shows a process of co-evolution. As the bacteria evolved to digest milk so the milk evolved to feed them. In the case of humans, the reason why we produce such a complex range of HMOs must be to specifically advantage B. infantis over other bacteria.

      So what do we get from the deal? Why do we want a single bug flourishing in our infant gut? The primary reason is probably competition. Human infants are born with a gut that is ostensibly sterile and provides an amazing opportunity for bacteria. It is warm, wet and full of a steady supply of nutrition from food and milk. It is also relatively unprotected by the naive infant immune system. From the moment the mother’s waters break, the baby starts swallowing a range of bacteria. The vagina is full of a carefully controlled mix of bacteria. And what strikes anyone watching a normal vaginal delivery is that the baby is born, face down, into a pile of faeces. It was my job as a medical student to hold a little gauze over the stool, protecting the child and to some extent the dignity of the mother (today, with our advancing knowledge of the microbiome, I wonder if it would have been better not to). Part of the role of breast milk then is to encourage the growth of ‘good’ bugs. This is the most obvious way in which B. infantis protects us: by binding to the cells lining the baby’s large intestine, preventing other, more harmful bacteria doing so. And crucially it seems to bind more strongly when grown on breast milk.

      It’s not just a matter of outcompeting the pathogens – B. infantis may keep them at bay with secretions. When grown on HMOs it produces short chain fatty acids (SCFAs). These are molecules that have become famous from their beneficial effects shown in adults eating a high-fibre diet, but they seem to be equally important in children. Some of them may directly kill harmful bacteria. Bruce describes this in terms of the concept of a ‘shelf stable baby’; preserved from the inside by the secretions of the friendly bacteria. Other SCFAs like acetate may feed the developing infant brain. This role in brain development may in part explain the huge complexity of the HMO in human milk compared even to our closest chimpanzee cousins.

      AT THE END OF MY CONVERSATION WITH MARK I ASKED IF HE HIMSELF HAD BEEN BREASTFED. ‘NO,’ HE REPLIED. ‘PERHAPS IF I HAD BEEN BREASTFED I’D HAVE BEEN A SURGEON.’

      There is a catalogue of other benefits, too. It’s been shown to be anti-inflammatory, specifically in infant gut tissue when compared to adults. Understanding of the development of the infant immune system is still in its early stages, but Bruce thinks that the specific culturing of B. infantis, and the relative lack of diversity in the infant gut, may be crucial to the development of a mature immune system. In fact he is evangelical about this. He believes that the current epidemic of asthma, allergy and atopic disease in the US may be largely due to the loss of B. infantis from infant guts.

      B. infantis also seems to reduce intestinal permeability, tightening up the joins between cells. Leaking infant guts may cause sickness directly but also affect the long-term development of the immune system. Evidence for this comes from an extraordinary study in Bangladesh. The dominant species in the stools of the infants in the study was B. infantis and they were 96 per cent breast-fed. The more B. infantis in the stool, the more weight gain and the better the responses to oral polio, tuberculosis and tetanus vaccines.

      And there are the extraordinary little considerations that B. infantis makes in order to be a good houseguest. Other similar species of bacteria are not directly harmful but they do digest human mucus. When they do this they accidentally produce sugars that are useable by dangerous bacteria. By contrast B. infantis leaves the complex sugars in human mucus intact, starving the pathogens.

      Just as the early efforts to understand the link between breast feeding and infant health required collaborations between chemists, physicians and microbiologists to make remarkable progress, Bruce German has forged a multidisciplinary team at UC Davis. While Bruce was starting to dissect the chemistry of milk in the lab, neonatologist Mark Underwood, at the UC Davis children’s hospital, was treating and studying children born long before 37 weeks’ gestation. Over 10 per cent of children are born prematurely in the United States and they face a few singular challenges. Inadequate lung development is the most immediate problem, but in the weeks spent in intensive care after birth a devastating condition called necrotising enterocolitis, or NEC, claims many infant lives. In NEC the tissue of the gut becomes inflamed and dies, allowing the contents of the gut to leak into the abdomen, causing massive infection. It affects approaching 10 per cent of infants who are born weighing less than 1,500 g and half of those affected will die. In the decades he has spent caring for premature babies, the death rates from NEC have not changed significantly, but some clues that B. infantis may help to reduce this death rate are starting to emerge. Breast milk improves outcomes in NEC and additionally, a lack of Bifidobacteria seems to increase risk.

      Neonatal intensive care is a dangerous place to be. Paradoxically this may be because it is too clean, or perhaps clean in the wrong way. Antibiotics and continuous cleaning keep Bifidobacteria at bay, but disease-causing organisms flourish in even the most fastidiously clean units. A trial is just starting at UC Davis but the evidence from other studies shows that administering B. infantis as a probiotic (a dietary supplement containing live bacteria that promotes health benefits) together with human breast milk serving as a prebiotic (a dietary supplement to stimulate the growth or activity of commensal microbes), may help to further reduce the incidence of NEC.

      Bruce is enthusiastic about the use of probiotics even in term infants and suggested that I give my own child some B. infantis prebiotic. I asked why simply breast feeding wouldn’t be enough. ‘Because B. infantis is extinct in much of the developed world. It’s not a bacteria which acquires resistance easily and particularly in the USA the use of formula milk for multiple generations has simply starved it out of existence.’

      Bruce has the infectious enthusiasm required for truly visionary science but I wondered if I was being seduced by his ideas too easily. The genetic case was certainly persuasive that B. infantis had co-evolved with breast milk to be the main colonist of the infant gut. Why else would it have the entire genetic toolkit to use molecules found only in human breast milk, molecules which humans were totally unable to digest? But I wanted a clinical perspective so I asked Mark Underwood for his view. Mark is no less visionary than Bruce but he has the sort of quiet, clinical caution that comes from being a doctor in a speciality where a lot of child patients die. He was no less enthusiastic than Bruce. He believes the evidence stacks up from all sides and he is about to start a trial of giving B. infantis as a probiotic in the neonatal ICU. From the second week of life, I have been giving Lyra once-daily B. infantis supplements sent by Bruce.

      At the end of my conversation with Mark I asked if he himself had been breast-fed. ‘No,’ he replied. ‘Perhaps if I had been breast-fed I’d have been a surgeon.’ He was being ironic: surgeons may think of themselves as being at the top of the tree, but physicians like to joke amongst themselves that surgeons are mere technicians. But his answer contained an interesting truth. He was a healthy, successful person. It is true that the mother–infant pair are what Bruce calls a ‘powerful Darwinian engine’ driving extraordinary evolutionary change. Together they have co-opted another species as the world’s most effective nanny, supporting brain development and the development of the immune system, as well as fighting pathogens. And loss of B. infantis from our ecosystem may well explain the rise in allergic and atopic disease. But contained in Mark’s answer is the idea that, despite multiple generations of formula-feeding and antibiotics rendering this seemingly vital bacteria functionally extinct, it’s possible to become a healthy professor without it. People continue to live longer and longer. The human body has extraordinary resilience and redundancy; regaining B. infantis in our infant guts may well have wide-ranging benefits, but it is testament to our adaptability that we can survive without it.

      GROWING UP, UP, UP …

      When it comes to growing up, the van Kleef-Bolton family from London are world-class. At 6 ft 5 in (195 cm) and 7 ft (213 cm) respectively, Keisha СКАЧАТЬ